Veterinarians occasionally use compounded preparations to meet a specific patient’s medical need. The purpose of this brochure, created jointly by the Animal Health Institute (AHI),
the American Veterinary Distributors Association (AVDA), and the American Veterinary Medical Association (AVMA), is to explain the Food and Drug Administration (FDA) requirements for compounding preparations for veterinary use and the distinction between drug products approved by the US FDA and compounded preparations.
At ProCompounding Pharmacy, we customize each prescription formulation specifically to each patients’ individual requirements. We strive to provide the utmost in customer care on every order. Please call us with any questions pertaining to your compounding request, we are here to discuss any questions or concerns you may have pertaining to your prescription.
- Enrofloxacain 11.35 mg/ml Oral Suspension
- Itraconzazole 20mg/ml Oral Suspension
- Erythromycin ethylsuccinate 46.8% and rifampin 5% Oral Suspension
- Estradiol 5mg/ml and progesterone 100mg/ml oil injection solution
- Progesterone 100mg/ml oil injection solution
- Aluminum Hydroxide oral suspension
- Calcitriol 4 nanograms/0.25 L
- Calcitriol 16 nanograms /ml oral oil solution
- Diethylstilbestrol Oral Capsules
- Protamine Zinc insulin 40 and 100 u/ml injection suspension
- Dexamethasone phosphate 0.1% ophthalmic ointment
- Idoxuridine 0.1% ophthalmic Solution
- Tacrolimus 0.03% ophthalmic ointment
- Tacrolimus 0.03% ophthalmic Solution
- Metronidazole Benzoate 125mg/ml Oral Suspension
- Acetyl-D-Glucosamine (N) 100mg/ml injection solution
- Hyaluronic Acid 10mg/ml injection
TRANSDERMAL MEDICATION : Have you ever thought about applying a transdermal preparation to the inside of an animal’s ear or another hairless area as an alternate route of systemic administration? It’s quick and easy, and many medications are compatible with transdermal bases. Transdermal delivery is particularly useful for animals who should not be stressed due to cardiovascular or hypertensive illness. Also, it is appreciated by owners who no longer have to deal with an animal who resists being medicated, and the resulting scratches! We can also prepare topical medications for application at the site of inflammation or infection.Advantages of Transdermal Dosage FormsVarious alternative dosage forms permit medication to be absorbed via non-oral routes to meet an animal’s specific needs. Although the parenteral and rectal routes are traditional alternatives to oral administration, transdermal absorption offers many advantages.
- When medication is absorbed directly into the bloodstream without first entering the gastrointestinal system, a smaller amount of active ingredient may be required for therapeutic effect.
- Direct application and absorption at the target site can mean higher tissue levels and lower blood levels of various medications. Side effects such as GI irritation can be eliminated.
- Various types of drug interactions may be avoided when one or more interacting medications are administered transdermally.
A substantial number of references exist in human medical literature with regard to the efficacy of transdermal administration of non-steroidal anti-inflammatory drugs and other types of analgesics, antiemetics, and other medications. We can compound transdermal and topical medications using a suitable base, and add penetrant enhancers if desired.
ANTI-INFECTIVE THERAPY :Antibiotic/Antifungal/Antiviral Therapy
Metronidazole is effective against a variety of obligate anaerobic bacteria as well as anaerobic protozoa such as Giardia and Trichomonas. “Various salts of metronidazole with improved palatability are now available for veterinary patients… Cats and birds accept the benzoate salt much more willingly than they accept metronidazole HCl and do not seem to be stressed by its administration.”Metronidazole should be used with caution in patients with hepatic dysfunction. Therapy should be promptly discontinued if abnormal neurological signs appear, including nystagmus, ataxia, seizures, and rigidity. All benzene moieties must be conjugated with glucuronide to facilitate elimination and this pathway is inefficient in cats. Therefore, doses of metronidazole benzoate above 200 mg/kg/day may produce signs of cumulative toxicity in cats within 48 to 72 hours.Compendium Dec. 2000: 22(12); pp. 1104, 1105, 1107, 1130Esophageal Strictures Secondary to Administration of Doxycycline Tablets
“The most common causes of esophageal strictures in dogs and cats are gastroesophageal reflux during anesthesia, persistent vomiting, or ingestion of foreign bodies or caustic agents. In humans, esophageal retention of oral medication is a common cause of severe esophagitis. Of the medications proven to lead to esophageal ulceration, doxycycline is most often implicated. It has been suggested that pill-induced esophagitis also could occur in small animals…” Drug-induced esophageal ulceration usually occurs when tablets are taken with little or no water and adhere to the esophageal mucosa. Once this occurs, flushing with large quantities of liquid fails to wash the medication into the stomach. Melendez et al. of Colorado State University College of Veterinary Medicine report on three cases of presumptive doxycycline-induced esophagitis in cats, with resultant stricture formation. All cats had been administered fractions of doxycycline tablets one to three weeks before presenting with a chief complaint of regurgitation. “Two of the cases developed regurgitation within 7 days after initiation of therapy with doxycycline. One cat, which was treated while at an animal shelter, was noted to be regurgitating the day that it was adopted, approximately 2 weeks after being treated with doxycycline. No other cause of esophageal stricture formation could be identified.” If a pet that has received a doxycycline tablet shows sign of esophagitis (dysphagia, excessive salivation, inappetence, and regurgitation), the doxycycline tablets should be discontinued. Suggested therapy for esophagitis includes sucralfate slurries, a prokinetic agent (i.e. cisapride) to increase lower esophageal sphincter tone, and anti-inflammatory doses of glucocorticoids to prevent stricture formation.
Feline Practice 28:2; 10-12 (Mar/Apr 2000)
Doxycycline can be compounded as a stable flavored liquid preparation or other palatable dosage form to meet the specific needs of each animal and owner.
Oral Itraconazole for Therapy of Dermatophytosis Caused by Microsporum canis
Itraconazole could be an effective alternative to griseofulvin that has toxic effects (particularly in puppies based on this author’s experience) and frequent therapeutic relapses. Itraconazole has also been used to successfully treat M. canis infection of cats and guinea pigs.
J Am Vet Med Assoc 1998;213:993-995
Chloramphenicol Suspension for Birds & Small Animals
by J. Terry McGrath, VMD, Pennsylvania
Since chloramphenicol palmitate is no longer commercially available, we contacted our compounding pharmacist for an alternative for use in our avian and other small patients, such as rabbits and rodents. The pharmacist prepared a cola flavored suspension containing 30 mg/ml of chloramphenicol palmitate, which could be administered using a small oral syringe. However, birds did not like the taste and it was reformulated into a tutti fruitti and pina colada syrup. The “animal appropriate” flavor has really helped with compliance, because now the birds and small animals like to take their medicine!
Note: To avoid potential antagonism, chloramphenicol should not be administered simultaneously with penicillin or streptomycin. Chloramphenicol-containing preparations should not be administered in conjunction with, or two hours prior to, the induction of general anesthesia with pentobarbital.
When administered orally in dogs, chloramphenicol is well-tolerated, has high clinical efficacy, and a low incidence of side effects. The recommended canine dosage is 25 mg/lb of body weight every six hours.
Precautions: Chloramphenicol should be administered cautiously to animals with hematopoietic dysfunction, or impaired kidney or liver function.
Intranasal Clotrimazole for Treatment of Nasal Aspergillosis in Dogs
“Treatment of nasal aspergillosis with systemic antifungal medications, such as thiabendazole, ketoconazole, and fluconazole, has been disappointing because the response rate is only 43 to 60%. Response to oral administration of itraconazole has been approximately 60 to 70%… Topical administration of the imidazoles, enilconazole, and clotrimazole is more effective than orally administered antifungal medications.”
Topical administration of clotrimazole resulted in resolution of clinical disease in 65% of dogs after 1 treatment and 87% of dogs after one or more treatments. Topical administration of clotrimazole, using either technique, was an effective treatment for nasal aspergillosis in dogs. Use of non-invasive intranasal infusion of clotrimazole eliminated the need for surgical trephination of frontal sinuses in many dogs and was associated with fewer complications. Nasal discharge ceased in most dogs 2 weeks after topical treatment, and the authors now recommend re-treatment with clotrimazole if nasal discharge has not improved 2 weeks after treatment.
“[Damage] of the cribriform plate may contraindicate use of topical treatment; complications arising from leakage of antifungal medications into the CNS in dogs with fungal rhinitis have not been evaluated.”
J Am Vet Med Assoc 1998 Aug 15;213(4):501-6 In order to access the PubMed abstract of this article, visit thiswebsite link.
J Am Anim Hosp Assoc 1998 Nov-Dec;34(6):487-92 In order to access the PubMed abstract of this article, visit thiswebsite link.
is a form of erythromycin with improved action against gram-negative organisms, resistance to acid degradation, improved tissue penetration, and a prolonged elimination half-life. Azithromycin shows potential for use in veterinary medicine, particularly in cats and certain avian and exotic species.
“Lacking the prokinetic action of erythromycin, azithromycin appears to cause fewer GI side effects and is generally well tolerated after oral administration. Cats appear to tolerate the drug particularly well… Animals with a history of arrhythmias should be monitored while receiving the drug. Some reduction in dose may be warranted in patients with hepatic or biliary dysfunction, although no reduction appears necessary in patients with renal dysfunction.” Please consult our compounding pharmacist regarding dosing.
Compendium of Continuing Education 23:3 (March 2001), pp. 242-7
Azithromycin for R. equi Infections in Foals
On the basis of pharmacokinetic values, minimum inhibitory concentrations of R. equi isolates, and drug concentrations in pulmonary epithelial lining fluid (PELF) and bronchoalveolar cells, a single daily oral dose of 10 mg/kg may be appropriate for treatment of R. equi infections in foals. Persistence of high azithromycin concentrations in PELF and bronchoalveolar cells 48 hours after discontinuation of administration suggests that after 5 daily doses, oral administration at 48-hour intervals may be adequate.
Am J Vet Res 2001 Dec;62(12):1870-5
In order to access the PubMed abstract of this article, visit this website link.
The Capsule Report, Mixed Practice/Exotic Edition Jan 2002;15, 10: page 1
Itraconazole/DMSO for Fungal Keratitis in Horses
Fungal keratitis is a serious complication of trauma to the eye. Approximately one-half of the cases of fungal infections have involved the use of eye ointments containing corticosteroids after trauma to the globe of the eye.
“Itraconazole is a third generation triazole that has superior penetration properties and a wide spectrum of activity. A 1% solution of itraconazole in a 30% DMSO and petroleum base has been shown to reach high concentrations within the stroma of the cornea when administered every 4 to 6 hours. In general, every 6 hours is suitable for all but Fusarium sp which requires every 4 hour administration.”
Disease which is rapidly ulcerating “should also receive treatment that helps block the enzymes (collagenase) responsible for ulceration. A 5% acetylcysteine solution and autologous serum in which 4 mg/ml of EDTA has been added has been recommended. These need to be instilled hourly for best effect. The antimicrobial can be added to the serum.”
This information has been abstracted from an article by Robert N. Oglesby, DVM, which appears on his webpage, “The Horseman’s Advisor.” For more information, references and complete text, see www.horseadvice.com/sbs/articles/diseases/skin/infectiouskeratitis.aspl
Idoxuridine Ophthalmic Drops for Cats
The ocular signs of feline herpesvirus I (FHV-1) infection include bilateral conjunctivitis, serous ocular discharge which may become mucoid or mucopurulent, and blepharospasm. If corneal involvement is present, topical antivirals are prescribed. Research indicates that idoxuridine is effective against FHV-1. Prolonged contact with the infected tissue is required. The 0.1% solution must be applied five times daily. Previously marketed as Stoxil®, the ophthalmic solution is not commercially available at this time.
www.eyevet.info/herpes.aspl (Michael Zigler, DVM, Cert.V.Ophthal)
Am J Vet Res 1989 Jan;50(1):158-60
Feline Ocular Toxoplasmosis
“The anterior uveitis seen in cats with a positive serum titer to Toxoplasma gondii may result from immune-mediated mechanisms and not the presence or replication of the organism itself. As a result, it is unclear whether systemic antitoxoplasmic therapy is beneficial in these cases.” Michael G. Davidson, DVM, of North Carolina State University, College of Veterinary Medicine reports in Vet Clin N Amer, Sep 2000, that he “usually treats cats with ocular lesions and concurrent systemic findings of toxoplasmosis with systemic clindamycin (12.5 mg/kg PO twice daily for 14-21 days) and anti-inflammatory therapy. Other sources recommend clindamycin 10-12.5 mg/kg every 12 hours for 4 weeks. Oral trimethoprim-sulfonamide combination therapy (15 mg/kg every 12 hours for 2 to 4 weeks) can also be used to treat toxoplasmosis but is less suitable because of potential side effects caused by folic acid deficiency in cats.2 In T gondii seropositive cats exhibiting anterior uveitis alone and with no systemic signs, Dr. Davidson recommends topical steroids and atropine alone. If the cat fails to respond to topical therapy alone within 1-3 weeks, systemic clindamycin should be added to the treatment regimen. The rationale for the use of corticosteroids is to suppress the damaging inflammation in the retina, which may affect vision. Corticosteroids are typically administered 1-2 days after antibiotic therapy has been initiated to allow adequate tissue levels of the antimicrobial agent to be achieved. [Dr. Davidson] does not recommend systemic steroids in cats with suspected ocular toxoplasmosis because of the risk of exacerbating systemic replication of T gondii.”1
Swift and aggressive treatment of uveitis is necessary to avoid such secondary complications as glaucoma, cataract formation, and retinal degeneration or detachment.3
1 The Capsule Report 19:10 (Jan 2001), p. 4
2, 3 Compendium of Continuing Education 23:3 (March 2001), pp. 258-66
BEHAVIORAL MEDICINE :Transdermal Treatment for Aggressive Cat
Donald Tummons, D.V.M.An 11 year-old male cat showed aggressive behavior towards other cats and also started urinary spraying. Buspirone 2.5mg/ml flavored suspension was tried. It was extremely difficult for the owner to give the oral suspension and after a few days the cat was vomiting the medication.Treatment
The owner was instructed to apply 0.1ml of transdermal buspirone 2.5mg/0.1ml pluronic lecithin organogel (PLO) topically inside the tip of the ear twice a day.Outcome
After the first dose, the owner noticed the medication made the cat too sleepy and the dose was decreased to 0.05ml (1.25mg of buspirone). The cat’s aggressive behavior has been controlled on the lower dose with a few exceptions and the owner then increased the dose to 2.5mg of buspirone for a couple of doses. The owner is amazed how easy it is to apply the medication.
Amitriptyline for Behavioral and Urinary Disorders
Amitriptyline hydrochloride is one of the most widely used tricyclic antidepressants (TCAs) in companion animal behavioral medicine, exerting antihistaminic, anti-inflammatory, analgesic, and antidepressant effects. Amitriptyline increases synaptic activity of serotonin and norepinephrine, has significant central and peripheral anticholinergic activity, and stimulates beta-adrenergic receptors in smooth muscle (e.g. the bladder), causing a decrease in smooth muscle excitability and a subsequent increase in bladder capacity and storage.
Although amitriptyline has been used successfully to treat behavior-related and urinary tract disorders in cats and dogs, the drug is not approved by the FDA for veterinary use and therefore is not available as a veterinary preparation.
Compendium 23(5) May 2001: 433-7
In animals, tricyclic antidepressants have actions similar to those of phenothiazines in altering avoidance behaviors. Imipramine has been used for the following indications:
Cats: urethral incompetence
Dogs: treatment of separation anxiety and other behaviors, cataplexy, urethral incompetence
Horses: narcolepsy and ejaculatory dysfunction
Naltrexone for Self-Mutilating Behavior
“Naltrexone may be useful in the treatment of self-mutilating or tail-chasing behaviors in dogs or cats… [A synthetic opiate antagonist,] naltrexone is generally considered to be contraindicated in patients physically dependent on opiate drugs, in hepatic failure or with acute hepatitis.”
Doses for Dogs:
As adjunctive therapy in behavior disorders:
For tail chasing or excessive licking: First give 0.01mg/kg SubQ of naloxone to determine if narcotic antagonists may be effective. If so, give naltrexone PO at 1 – 2 mg/kg daily. Long-term therapy may be required. (Crowill-Davis 1992)
For the adjunctive treatment of acral pruritic dermatitis:
2.2mg/kg PO once daily for one month trial. Some dogs exhibit drowsiness and minor changes in behavior. 50-60% of patients have benefited… (Rosychuck 1991)
Canine Acral Lick Dermatitis
involves excessive licking of the paws or flank, even to the point of self-mutilation, and can produce ulcerations and infections that require medical treatment. Based on patterns of behavior and response to medication, veterinary scientists propose that canine acral lick dermatitis, also known as canine compulsive disorder (CCD), is an animal model of human obsessive-compulsive disorder. A randomized, placebo-controlled, double-blind crossover clinical study evaluated the efficacy of the medication clomipramine for treatment of CCD. Fifty one dogs with CCD were given clomipramine 3 mg/kg [1.3 mg/lb] of body weight orally every 12 hours for 4 weeks and then placebo for 4 weeks. While drug therapy can be helpful, therapy may need to include behavior modification to optimally manage CCD.
J Am Vet Med Assoc 1998 Dec 15;213(12):1760-6 In order to access the PubMed abstract of this article, visit thiswebsite link.
Arch Gen Psychiatry 1992 Jul;49(7):517-21 In order to access the PubMed abstract of this article, visit thiswebsite link.
Fluoxetine for Refractory Owner-Directed Dominance Aggression
Evidence suggests that social dominance aggression may be modulated by serotonergic mechanisms. Fluoxetine (Prozac®), a specific inhibitor of serotonin reuptake, is a popular human antidepressant which has been used successfully to decrease social aggression in dogs and monkeys.
J Am Vet Med Assoc 1996;209:1585-1587 In order to access the PubMed abstract of this article, visit thiswebsite link.
Fluoxetine for Urine Spraying in Cats
Administration of fluoxetine hydrochloride for treatment of urine spraying in cats can be expected to considerably reduce the rate of urine marking. Pryor et al. recommend that most cats should be treated more than eight weeks before treatment is withdrawn. Cats that vertically marked a mean of > or = 3 times per week were treated for 8 weeks with fluoxetine (1mg/kg PO daily- dosage individualized for each cat by a compounding pharmacy) or fish-flavored liquid placebo. When treatment was discontinued after 8 weeks, the spraying rate of cats that had received treatment varied. The main adverse reaction to the drug was a reduction in food intake, which was observed in 4 of 9 treated cats.
J Am Vet Med Assoc 2001 Dec 1;219(11):1557-61 In order to access the PubMed abstract of this article, visit thiswebsite link.
Inappropriate Elimination in Cats: Fluorescein to Find the Culprit
In a multi-cat household, it is important to determine which cat is inappropriately eliminating so that the proper intervention can be made. Even if one cat is observed marking or urinating outside the box, it does not rule out the possibility that other cats are also behaving inappropriately. When it is necessary to identify which cat in a multi-cat household is spraying or inappropriately eliminating, fluorescein can be orally administered once daily in the evening with food for three days. That cat’s urine will fluoresce under ultraviolet light for approximately 24 hours. To detect urine containing the fluorescein indicator, the client needs to scan the household with a commercial black light or black light purchased from a novelty store. Although urine will commonly glow, fluorescein treated urine fluoresces a characteristic bright yellow. Caution clients that they may reveal previously undiscovered sites of elimination; advise them not to become alarmed or angry. By administering the dye to different cats at two day intervals, the culprit can be identified.
Pharmacological support for urine spraying or marking is usually needed only for cases with underlying anxiety or problems with social interactions between cats (clomipramine), or for cats with interstitial cystitis (amitriptyline, doxepin). Administration of fluoxetine hydrochloride for treatment of urine spraying in cats may also considerably reduce the rate of urine marking.
Cyproheptadine to Control Urine Spraying and as an Antipruritic in Cats
A 10-year-old castrated male domestic cat was admitted to the hospital at the School of Veterinary Medicine, Tufts University. A diagnosis of territorial urine marking was made. Treatment included behavior modification and the administration of cyproheptadine, which resulted in the immediate arrest of undesirable urine marking. Cyproheptadine administration was adjusted to determine the lowest dosage that effectively maintained the cat’s consistent use of the litter box. It was recommended to continue cyproheptadine administration for at least 1 year before any attempt to withdraw its use. Another study recommended a dose of 2 mg, p.o., every 12 hours. This antihistamine, also prescribed for its appetite stimulant effects in cats, has antiandrogenic effects in other species.
J Am Vet Med Assoc 1999 Aug 15;215(4):501-2, 482 In order to access the PubMed abstract of this article, visit thiswebsite link.
J Am Vet Med Assoc 1999 Feb 1;214(3):369-71, 351-2 In order to access the PubMed abstract of this article, visit thiswebsite link.
Cyproheptadine hydrochloride was administered to 20 presumed or proven allergic cats to determine its efficacy in controlling pruritus. Each cat received 2 mg, orally, every 12 hours. The pruritus was satisfactorily controlled in 9 cats. Side effects were seen in 8 cats, and included polyphagia, sedation, vocalization, affectionate behavior, and vomiting.
Can Vet J 1998 Oct;39(10):634-7 In order to access the PubMed abstract of this article, visit thiswebsite link.
Clomipramine for Feline Anxiety
A study of 11 cats assessed the clinical response to a treatment regimen that included clomipramine and behavior modification in cats diagnosed with anxiety-related or obsessive-compulsive disorders. Presenting signs were urine spraying in seven cases, overgrooming in three and excessive vocalization in one. Clomipramine was administered orally once daily, with a mean starting dose of 0.4 mg/kg. If necessary, the dose was adjusted according to the clinical response of each cat. The average maintenance dosage was 0.3 mg/kg once daily. The researchers concluded that clomipramine was effective in controlling the signs of anxiety-related and obsessive-compulsive disorders in 10 of 10 assessable cases when used in combination with behavior modification, and the drug was well tolerated.
Aust Vet J 1998 May;76(5):317-21 In order to access the PubMed abstract of this article, visit thiswebsite link.
is a monoamine oxidase (MAO) inhibitor indicated for use in dogs to control signs associated with canine cognitive dysfunction syndrome and uncomplicated pituitary-dependent hyperadrenocorticism (PDH). Studies suggest that selegiline may enhance survival rates. The recommended dose for cognitive dysfunction is 0.5 to 1 mg/kg, and for PDH is 1 mg/kg, orally each morning. If no improvement is seen after 2 months, the dose can be increased to the maximum of 2mg/kg/day. If there is no clinical improvement after 1 month at 2mg/kg/day, alternative therapy or further evaluation should be considered. “Overall, selegiline is well tolerated… Gastrointestinal disturbances, particularly vomiting and diarrhea, are the most common side effects reported. Diarrhea may resolve when the drug is discontinued or the dose decreased. Other adverse effects include hyperactivity, agitation, restlessness, and insomnia. A dose reduction or discontinuation of therapy also resolves these problems.”
Compendium March 2000; 22(3):204-5
CARDIOLOGY / HYPERTENSION :Enalapril for Cardiomyopathy and CHF“Enalapril maleate is an angiotensin-converting enzyme (ACE) inhibitor labeled to treat mild to severe heart failure in dogs.” Research has shown that enalapril in combination with diuretics – with or without digitalis glycosides – “produces statistically significant clinical improvement in dogs with advanced heart failure due to mitral regurgitation or dilated cardiomyopathy” and has demonstrated “beneficial hemodynamic and clinical effects of adding enalapril to conventional therapy for dogs with CHF… Dogs treated with enalapril and conventional CHF therapy survived two times as long as did those receiving standard therapy alone.”Enalapril has also “been effective in treating cardiomyopathy and CHF in cats and ferrets, and its effects on blood pressure in horses and camels have been studied.” Because enalapril is a prodrug and can not be converted to its active form enalaprilat in patients with severe liver dysfunction, captopril or lisinopril might be a better choice in those patients. Renal function should be checked before starting enalapril therapy and at least every two months thereafter. The most common side effects are gastrointestinal, but there have been reports of enalapril-induced cough in dogs and a bird. Hypotension is a major concern if overdose occurs. NSAIDs, including aspirin, may reduce enalapril’s effect. The injectable form (enalaprilat) should not be given orally because it is very poorly absorbed.“The recommended dose for enalapril in dogs is 0.5 mg/kg orally every 12 to 24 hours. The dose for cats is 0.25 to 0.5 mg/kg orally every 12 to 24 hours.”Compendium, Dec. 1999
Amlodipine to Treat Feline Systemic Hypertension
Amlodipine, a calcium channel blocker, has an antihypertensive effect in cats with coexistent systemic hypertension and renal insufficiency. Its use may improve the prognosis for cats with systemic hypertension by decreasing the risk of ocular injury or neurologic complications induced by high blood pressure (BP). In a retrospective study, medical records from 69 cats with systemic hypertension and hypertensive retinopathy were reviewed. 68.1% of the cats were referred because of vision loss; retinal detachment, hemorrhage, edema, and degeneration were common findings. Amlodipine decreased BP in 31 of 32 cats and improved ocular signs in 18 of 26 cats. Primary hypertension in cats may be more common than currently recognized.
In a study at the Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, amlodipine was shown to be a safe and effective once-daily antihypertensive agent when administered to cats at a dosage of 0.18 +/- 0.03 mg/kg daily as monotherapy. Researchers at the Department of Medical Sciences, University of Wisconsin-Madison, administered amlodipine at an oral daily dosage of 0.625 mg per cat (range = 0.08 to 0.23 mg/kg body weight). Average indirect systolic blood pressure measurements in those 12 cases decreased significantly from 198 to 155 mmHg during amlodipine treatment. Significant changes in body weight and serum creatinine and potassium concentrations were not detected.
Relationship between ocular lesions and hypertension
Retinal lesions, caused predominantly by choroidal injury, are common in cats with hypertension. Hypertension should be considered in older cats with acute onset of blindness; retinal edema, hemorrhage, or detachment; cardiac disease; or neurologic abnormalities. Cats with hypertension-induced ocular disease should be evaluated for renal failure, hyperthyroidism, diabetes mellitus, and cardiac abnormalities. Blood pressure measurements and funduscopic evaluations should be performed routinely in cats at risk for hypertension (preexisting renal disease, hyperthyroidism, and age > 10 years).
Am J Vet Res 2002 Jun;63(6):833-9 In order to access the PubMed abstract of this article, visit thiswebsite link.
J Am Vet Med Assoc 2000 Sep 1;217(5):695-702 In order to access the PubMed abstract of this article, visit thiswebsite link.
J Vet Intern Med 1998 May-Jun;12(3):157-62 In order to access the PubMed abstract of this article, visit thiswebsite link.
J Am Anim Hosp Assoc 1997 May-Jun;33(3):226-34 In order to access the PubMed abstract of this article, visit thiswebsite link.
DERMATOLOGICS : Alternative Therapies for Atopy
Dogs with atopic dermatitis (AD) often have concurrent allergies and are prone to relapsing skin and ear infections, which significantly contribute to their discomfort level. Much research has been done in recent years to identify effective and safe alternative treatments. Percutaneous absorption of allergens may be the most relevant route of exposure in dogs. Topical therapy may reduce the amount of allergen absorption through the skin. Several preparations, including glucocorticoids and anesthetics, can be used to reduce pruritus and provide analgesia.
Cyclosporine, misoprostol, pentoxifylline, and various antihistamines have been effective.Compendium 2001 May 23(5):454-60 Tetracycline/Niacinamide for Dermatology
The combination of tetracycline and niacinamide is being used for a continually expanding list of dermatologic disorders thought to be of immune-mediated origin. Diseases that may be controlled with this combination include discoid lupus erythematosus, pemphigus erythematosus, vesicular cutaneous lupus erythematosus (idiopathic ulcerative dermatosis) in Collies and Shetland Sheepdogs, pemphigus foliaceus, lupoid onychodystrophy, metatarsal fistulae in German Shepherds, sterile panniculitis, sterile granulomatous/pyogranulomatous dermatitis, vasculitis, cutaneous histiocytosis, idiopathic lymphocytic/plasmacytic ear margin dermatitis, and nodular granulomatous episcleral keratitis.The Capsule Report (Small Animal/Exotic Edition) 21:9, December 2002, reporting on Proceedings of the Friskies Pet Care Symposium 10:01
J Am Anim Hosp Assoc 1997 Nov-Dec;33(6):540-3 In order to access the PubMed abstract of this article, visit thiswebsite link.
J Am Vet Med Assoc 1992 May 15;200(10):1497-500 In order to access the PubMed abstract of this article, visit thiswebsite link.
Antihistamines in Horses
Practitioners may prefer to use antihistamines to reduce urticarial reactions and reduce pruritus in horses because these drugs usually have fewer side effects than steroids. The American Quarter Horse Association recommends a 10 day withdrawal prior to any competition.
Vet Prac News, Apr 2001
Prednisone Administered as a Transdermal Gel to Treat Allergic Dermatitis in a Cat
Submitted by Janna L. Love, Pharm.D.
A 5 y.o. female feline presented with allergic dermatitis accompanied by severe scratching and hair loss.
The cat had previously been treated with oral prednisone tablets. As the owner was unable to “pill the cat”, she had tried to crush the tablets and mix with milk or tuna juice, but the cat still would not take the medication.
It has been our experience that transdermal gels work wonderfully in cats. An owner does not have to fight the animal to get a tablet down the cat’s throat, and does not have to worry about whether the animal has received the correct dose, as the prescribed amount of gel can be massaged into the vascular surface inside the cat’s ear.
The veterinarian prescribed Prednisone 5 mg/0.1 ml in a transdermal gel. We dispensed 3 ml, with instructions to apply 0.1 ml (5 mg) daily to the inside of the cat’s ear. The benefits of transdermal administration include the ability to reliably administer the prescribed dose, and ease of administration to a calm, relaxed cat.
The therapy was very successful. The cat’s dermatitis resolved and the hair began to regrow within a few weeks. There were no complications and no modification in dosage was necessary. The owner periodically uses the preparation when she first notices signs of a relapse. Relapses have promptly resolved with transdermal prednisone therapy.
ENDOCRINOLOGY :PZI and Low-Dose Insulin
The commercial production of traditional beef &/or pork insulins has declined as most human diabetic patients (the majority of the consumers) are being switched to human insulin products because of the reduced risk of allergic reactions. Protamine zinc insulin occurs as a sterile suspension of insulin modified by the addition of protamine sulfate and zinc chloride, and has a long duration of action (up to 30 hours). Therefore, treatment of many dogs and cats has been accomplished with once daily dosing of PZI.
U-20 and U-40 insulin allow for more accurate measurement of smaller doses required by many pets and birds. Use of U-100 insulin can result in morbidity or mortality caused by dosing errors.Please call our compounding pharmacy for more information about these insulin preparations for animals.Oral Anti-Diabetic Drugs
“may be appropriate for cats that are in good overall health with early or mild clinical signs of diabetes and those with owners who are unwilling or unable to administer insulin injections.”1 The oral hypoglycemic medication, glipizide, provides a viable therapeutic alternative to conventional insulin therapy with a positive therapeutic response in approximately 50% of diabetic cats with non-insulin-dependent disease. Response to glipizide therapy or lack thereof usually is evident within the first 4 to 6 weeks of treatment. Adverse side effects occurred in less than 10% of patients. The existence of residual beta cell function is necessary for response to glipizide therapy. Discontinuation of diabetogenic medications that may be contributing to insulin resistance is important.2According to Deborah S. Greco, DVM, Ph.D., diplomate ACVIM, glipizide has been used successfully to treat diabetes mellitus in cats at a dosage of 2.5 to 5 mg two times daily, when combined with dietary fiber therapy. Dr. Greco recommends evaluating the patient weekly or every two weeks for a period of 2 to 3 months. If the fasting blood sugar decreases to less than 200 mg/dL, the glipizide should be continued at the same dosage and the cat reevaluated in 3 to 6 months. If the fasting blood glucose remains >200 mg/dL after 2 to 3 months of therapy and the cat is still symptomatic (polyuria, polydipsia, weight loss), glipizide should be discontinued and insulin therapy instituted. If the blood glucose remains >200 mg/dL and the cat becomes asymptomatic, glipizide should be continued indefinitely and the cat rechecked in 3-6 months.3
1 Compendium 23(7), July 2001, 633-640
2 Vet Clin North Am Small Anim Pract 1995 May;25(3):599-615
In order to access the PubMed abstract of this article, visit thiswebsite link.
3 presented at the 1999 Southern California VMA Seminar and the 116th Indiana VMA Seminar
Methimazole for Feline Hyperthyroid Disease
“Methimazole is the drug of choice for the medical management of feline hyperthyroid disease. It is safer and more potent than propylthiouracil in blocking thyroid hormone synthesis. Use of the drug generally will bring serum T4 into normal ranges within 2 to 3 weeks… Adverse effects have been observed in approximately 15% of cats and generally are transient. Anorexia, vomiting, and transient lethargy have been reported. Serum antinuclear antibodies develop in many cats with long-term use of the drug. A glucocorticoid-responsive pruritus involving the face, ears, and neck may occur. In less than 2% of cases, thrombocytopenia or agranulocytosis have been reported in cats treated with [methimazole]. Withdrawal of the drug and provision of care for thrombocytopenia or agranulocytosis generally results in resolution… Cats on chronic methimazole therapy should be rechecked every 3 to 6 months to assay serum T4 levels and to check for signs of drug toxicity.”
Handbook of Veterinary Drugs, 2nd edition, ©1998, pp. 239-240
According to the International Journal of Pharmaceutical Compounding (Vol. 5, No. 2, March/April 2001, p. 96), “it could be theorized that transdermal administration would produce a … higher blood level of methimazole than that resulting from oral administration of the drug. A higher blood level of [methimazole] might result in a slightly greater risk of adverse effects, so drug therapy might need to be initiated at a slightly lower dose than that of the traditional oral dose.” The author of the article (GiGi Davidson, R.Ph., DICVP, North Carolina State University, College of Veterinary Medicine) states that anecdotal evidence indicates that this is true of “most transdermally administered doses of methimazole. The most measurable parameter for efficacy is the response of the serum T4 level.”
Note: Methimazole is also used to decrease renal toxicity of cisplatin in dogs.
Transdermal Methimazole Applied to Ear of Hyperthyroid Cats
Francis Arsenault, D.V.M., New Brunswick
The following six cats have received methimazole in a pluronic lecithin organogel (PLO) which the owners apply to the inner side of the ear. Overall, we have found this to be very effective therapy with good compliance. Transdermal administration can be particularly helpful for owners who have arthritis and those who have great difficulty “pilling” the cat. Methimazole doses have ranged from 2.5mg to 12.5 mg daily, divided into two doses.
Cat #1 (S.A.): 17 years old, has been on methimazole 1.25mg/0.1 ml PLO to inside of ear twice daily for nine months. The owner reports that the medicine is easy to administer and absorbs well. I am pleased with the clinical results.
Cat #2 (A.L.): 18 years old, has been using methimazole for six months. This cat was started on 3.5mg/0.1ml PLO BID. Several dosage adjustments were necessary. We increased the concentration of the transdermal gel to 5.0mg/0.1ml PLO, and the owner now applies 7.5mg/0.15ml PLO in the AM and 5mg/0.1ml in the PM. She places plastic wrap over her finger before applying the medication, which she has found to be much easier to use than pills, with no stress to the pet. She states the measurements on the topical dispenser are easy to read, and she needs to wash the cat’s ear to remove the coating left by the medication.
Cat #3 (B.M.): was started on methimazole eight months ago at 5mg/0.1ml PLO BID. The dose was decreased to 2.5mg BID. The cat’s owner stated the medication was very easy to use. B.M. improved clinically and gained weight, and is no longer on the med.
Cat #4 (S.O.): used medication once only.
Cat #5 (D.O.): same owner as cat #4, received methimazole 2.5mg/0.05ml PLO BID for two months. No longer on medication.
Cat #6 (M.B.): 19 years old, has received methimazole 1.25mg/0.1ml PLO BID for four months. The owner says the medication is easy to apply, and alternates ears. It is necessary to wipe the ear each day as the medication does leave a residue.
Adrenal Disease in Male Ferrets
Adrenal gland disease is a common problem in middle-aged to older ferrets. The disease results in one or both of the adrenal glands producing abnormal amounts of androgens and/or estrogens, and can cause hair loss, itching, vulvar enlargement in females, prostate enlargement in male ferrets which can block the flow of urine, and in rare cases, bone marrow suppression. Although not usually a serious health concern, ferrets may have no relief from the itching that is associated with this disease if it is not treated.
Flutamide is an androgen blocker that may help relieve prostatic enlargement. It is dosed at 10 mg/kg, PO, every 12-24 hours. Liver enzymes should be checked at one month and every six months thereafter. Mitotane may be effective in younger ferrets but may cause nausea and lethargy. Ketoconazole is usually ineffective.1
1 Evelyn Ivey, DVM, Dip ABVP, San Diego Co VMA Conf Procd, Sep 2000
Mitotane for Canine Hyperadrenocorticism
In veterinary medicine, mitotane is used primarily for the medical treatment of pituitary-dependent hyper-adrenocorticism (PDH) and palliative therapy of adrenal carcinoma, usually in dogs. Systemic drug availability has been found to be very poor from intact tablets in fasted dogs, and best when the powdered drug is mixed in oil and poured on dog food. The interaction between food and mitotane probably contributes to the variation in clinical response of dogs treated with the drug, because it appears that the efficacy is improved considerably when the drug is given with food. Because of the potentially severe toxicity associated with mitotane, clients should be instructed to wear gloves during and wash their hands after administering the medication, and to keep the medication out of reach of children or pets. Dogs with concurrent diabetes mellitus may have rapidly changing insulin requirements during the initial treatment period, and should be closely monitored until they are clinically stable. Clients should be advised of the symptoms of acute hypoadrenocorticism. Because of the potential severe toxicity associated with mitotane, clients should be instructed to wash their hands after administration and to keep the medication out of reach of children or pets.
Res Vet Sci 1987 Sep;43(2):160-5
Veterinary Drug Handbook, 2nd Edition, by Donald C. Plumb
OTITIS :Therapy for Chronic Canine Otitis
Treatment errors, over and under treatment, or inappropriate use of antimicrobial medication can result in a chronically diseased ear. The key to successful management of chronic canine otitis is early intervention, identifying a cause of the condition, and employing specific and appropriate therapy.Ears with highly proliferative, chronic disease require deep cleaning and flushing before any topical therapy can be expected to help resolve the condition. Should a myringotomy be performed, the contents of the middle ear can be aspirated as soon as rupture occurs, and the middle ear can be flushed with normal saline or Tris-EDTA using a feline, open-tipped urinary catheter. “Just before the animal wakes, Tris-EDTA and a topical antimicrobial solution should be instilled and a parenteral prednisolone administered.””The pathogens isolated most frequently from chronic external and middle-ear infections include Staphylococcus intermedius, Malassezia pachydermatis, Pseudomonas species, Proteus species, Escherichia coli, and enterococcus. Selection of both systemic and topical antimicrobial medication is based on cytologic evaluation and culture and sensitivity results. Systemic antibiotics are mandatory… Treatment should continue until the infection is resolved (a minimum of 4 weeks). It is not uncommon for treatment of otitis media to continue uninterrupted for 8 to 12 weeks.”Patricia D. White, DVM, MS of Atlanta Veterinary Skin & Allergy Clinic suggests that several compounded preparations may be appropriate.Compendium on Continuing Education 21:8 August 1999, pg 716-28
Importance of Medication Vehicle
Topical antimicrobial therapy is an important part of the treatment regimen, and the vehicle is as important as the active ingredient. Most otic preparations are combination drugs (glucocorticoid plus antibiotic) in an oil or ointment base. Oils and ointments are occlusive, may hold or trap exudate, and may increase the risk of ototoxicity; such preparations are not desirable in cases of chronic otitis in which a moist exudate is present, the canal is stenotic, or the eardrum may be ruptured. The goal of treating a wet ear is to dry it. Solutions and suspensions are primarily composed of water; may contain an astringent (e.g., aluminum acetate); and are designed to evaporate over time, thus helping to dry the ear.” Topical antibiotics that are selected initially should be adjusted when the culture and sensitivity results are known.
“There is no single topical otic preparation that will satisfactorily treat all conditions. Practitioners tend to dispense a product based on clinical impressions or pick a favorite product rather than selecting one that has specific application for the current condition.” Direct application of medication to the ear canal will result in a higher concentration than that obtained with systemic medication.
Once you have identified the problem, we can compound an otic preparation to most appropriately treat each animal.
Compendium on Continuing Education 21:8 August 1999, pgs. 716-728
Antimicrobial/Anti-inflammatory Otic Suspensions, Anhydrous Preparations without Aminoglycosides
It is desirable to move away from commercially available aminoglycoside- antifungal-steroid otic preparations to avoid animoglycoside induced ototoxicity. Use of a formulation that substitutes a fluoroquinolone for an aminoglycoside constitutes a more effective and less toxic therapy, and is preferred if a tympanum rupture is expected. The efficacy and tolerability of a fluoroquinolone-clotrimazole-dexamethasone (FCD) otic suspension (10 drops per affected ear once daily) was compared with a standard topical treatment containing polymyxin B, miconazole and prednisolone (PMP) in a total of 140 dogs with clinical signs of acute or subacute otitis externa, Staphylococcus, Pseudomonas, Enterobacteriaceae and Malassezia were isolated from samples taken at inclusion. Each group received treatment for 7 or 14 days according to the clinical outcome on day 7. Treatments were equally effective, with a cure rate of 58.3% for the FCD prep and 41.2% for the PMP combination. Both medications were equally well tolerated by dogs, but FCD was superior in terms of pain relief, decrease in pus quantity and smell, response rate and investigator’s assessment on day 14.
Vet Dermatol 2005 Oct;16(5):299-307 Click citation for abstract.
While it is a common practice in some veterinary offices to add dexamethasone injection to clotrimazole solution to create an otic preparation with both antifungal and anti-inflammatory properties, it is more desirable to use an anhydrous preparation in the ear to reduce the risk of bacterial growth in the warm, moist environment. Anhydrous preparations also tend to have longer shelf lives. Avoid using products such as miconazole solution which has a high alcohol concentration to avoid irritating a sensitive ear.
Contact our compounding pharmacy for anhydrous otic preparations.
Helpful Hints Regarding Otitis Therapy
Ototoxicity manifested as deafness or vestibular toxicity is a potential adverse effect of some medications used to treat otitis, such as aminoglycosides (tobramycin, gentamicin, amikacin and neomycin) and chloramphenicol. Numerous alternatives exist.
Enrofloxacin, a fluoroquinolone effective against Pseudomonas species, can be compounded as a solution and applied to the ear canal twice daily. “Topical enrofloxacin may achieve a higher antibiotic concentration at the site more economically than systemic medication.”
Silver sulfadiazine is effective in vitro against Pseudomonas species, Staph aureus, Proteus species, and others; a 0.1% to 1% emulsion every 12 hours is adequate to kill Pseudomonas.
Topical otic products may contain potent glucocorticoids in ointment or oil bases. However, solutions may be a preferable vehicle, and it may be advisable to use a less potent steroid because the degree of absorption of topical steroids can not be controlled. We can compound a preparation containing your choice of steroid in the most appropriate vehicle to treat the condition.
“Commercial otic drying agents should be avoided in inflamed, chronically diseased ears because most contain isopropyl alcohol and varying concentrations of benzoic, acetic, salicylic, or boric acid. Each of these products individually can be extremely irritating to an already traumatized epithelium.”
Acetic acid solution can be used to decrease the bacterial population by lowering the pH within the ear canal. Pseudomonas can be killed by 1 minute of contact with a 2% solution. This treatment is especially beneficial when the organism is resistant to other antibacterials. Staph and Strep may be killed by 5 minutes of contact with a 5% solution, according to Kirk’s Current Veterinary Therapy XII Small Animal Practice. However, inflammation (which can be severe) is an occasional side effect of treatment with acetic acid concentrations higher than 2.5%.
Compendium on Continuing Education 21:8 August 1999, pgs. 716-728
Kirk’s Current Veterinary Therapy XII Small Animal Practice, 1995, Bonagura & Kirk, ed.
Treatment of Canine Otitis with Norfloxacin 1% & Ketoconazole 1% by T. D. Flack, D.V.M. Scottsdale, AZ
The common therapy for fungal otitis externa in dogs utilizes an antifungal and topical steroid, sometimes in combination with systemic antibiotics. The three organisms which have been isolated and are thought to be the most common pathogens in recurrent canine otitis externa are Malassezia, Pseudomonas, and Proteus spp. Using a fluoroquinolone along with an antifungal, we are able to have good coverage on all virulent pathogens. For treatment of resistant infections, the synergism of norfloxacin and ketoconazole provides a broader spectrum of coverage than many other therapies, as ketoconazole is a more active antifungal than clotrimazole. We have utilized a compounded otic gel containing norfloxacin 1% and ketoconazole 1% more than 20 times with a very high success rate.
Infectious otitis externa is a common disease in dogs. Systemic antibiotic therapy is not always required. Thirty-six dogs of mixed sex, breed, and age were treated for… the purpose of evaluating the efficacy of a ketoconazole 1% and norfloxacin 1% otic gel… Treatment consisted of 0.5 to 1.0 ml of the otic gel in each affected ear twice a day for 7 days. Results showed 91.66% satisfactory responses at 7 and 14 days treatment… Failures (8.33%) were related to Staphylococcus associated with Proteus, Malassezia, and Candida… The 7-day treatment was successful in 21 cases. However, since 12 dogs required 14 days of treatment, it would be sensible to recommend a 14-day therapy.”
Canine Practice, Vol. 21, No. 2, pp. 26-28
Tris-EDTA Solution for Canine Otitis
Richard E. Wooley, D.V.M., Ph.D., Harry W. Dickerson, B.V.Sc., Ph.D.,
and William R. Engen, D.V.M.,
Department of Medical Microbiology, College of Veterinary Medicine, Univ. of Georgia, Athens
authors reported the successful use of Tris-EDTA in the treatment of otitis externa. In 24 dogs with clinical otitis, the Tris-EDTA (tris[hydroxymethyl] aminomethane and ethylenediaminetetraacetate) combination was tested against Bacillus spp., Staphylococcus aureus, Candida spp., Pseudomonas aeruginosa, Esherichia coli, Proteus vulgaris, Trichosporon spp., and an a-streptococcus. “Fifteen of the 24 cases were acute; all were evaluated with bacterial culture before and after treatment. The treatment consisted of applying lavage solution to the ears t.i.d. until resolution or for three weeks if there was no clinical response. Dogs were examined for irritation of the ears after treatment… 23 of 24 cases were resolved; no adverse effects were seen, but duration of follow-up was not specified. The case that failed to respond was a chronic, mixed infection of E. Coli and Proteus spp.; inflammation was reduced, but the infection persisted. Most cases responded within one week, but P. aeruginosa infections required one to three weeks of treatment.”
Veterinary Forum, June 1999, p. 52
Tris-EDTA solution (buffered to pH 8.0) has a direct bactericidal effect on some bacteria by chelating metal ions in the cell wall. “Dogs with chronic disease (e.g. atopy, idiopathic seborrhea) will be predisposed to recurrent otitis; a topical antibiotic solution or Tris-EDTA used two to three times weekly may prevent an infection from occurring with each flare-up of the primary disease.”
The bactericidal effects of Tris-EDTA are synergistic with aminoglycosides. Although an antibiotic can be added to the Tris-EDTA solution, Patricia D. White, DVM, MS states that she prefers to use Tris-EDTA 5 to 10 minutes before the topical antibiotic. The Tris-EDTA/antibiotic combination is ineffective against yeast.
Compendium on Continuing Education 21:8 Aug. 1999, pgs. 716-728
PAIN MANAGEMENT: Pain Management in Cats
Pharmacokinetic data developed in other species cannot be safely extrapolated to the cat. Feline deficiency of glucuronidation pathways results in slow metabolism of several NSAIDs, which prolongs the duration of effect and may lead to drug accumulation and toxicity.Meloxicam, a COX2 selective NSAID, has demonstrated clinical efficacy for chronic pain, musculoskeletal pain, and routine soft tissue surgery with few side effects. Based on clinical experience, Lascelles of NCSU College of Veterinary Medicine, now recommends oral meloxicam doses for cats that are less than previously reported in the literature (0.1 mg/kg PO on day 1 followed by 0.05 mg/kg PO daily for 4-6 days, then 0.025 mg/kg daily for 10 days, then lowest effective dose).1Five days of oral treatment with meloxicam or ketoprofen for cats with painful locomotor disorders provided similar analgesia2, but meloxicam drops were more palatable than ketoprofen tablets. Appropriately flavored preparations in a convenient dosage form are easier for owners to administer and allow for accurate dosing.According to Robertson and Taylor3, opioids have an unjustified reputation for causing mania in cats, but with refinements in dosing they are now used successfully in this species. The mu-opioid agonists are generally considered the best analgesics. Morphine (0.1–0.3 mg/kg) is effective in a clinical setting. Oxymorphone and hydromorphone (0.05–0.1 mg/kg) are widely used in the USA. These opioids are more potent (up to 10 times), and longer acting than morphine in cats. Buprenorphine (0.01–0.02 mg/kg), a partial mu-agonist, is the most popular opioid used in small animal practice in the UK, other parts of Europe, Australia and South Africa. In clinical studies it has produced better analgesia than several other opioids and appears to be highly suitable for perioperative pain management in cats.Amitriptyline (starting dose 2.5 mg/kg PO, once daily) has been used to treat feline interstitial cystitis with few side effects, and there are anecdotal reports of its use for cancer and neuropathic pain management.
Some of the less conventional analgesics including the tricyclic anti-depressants and gabapentin may prove to play a useful role in chronic pain management, but controlled clinical trials are needed to establish the best doses for maximum efficacy. Other less traditional analgesics such as ketamine and local anesthetics are also used for clinical pain management. The transmucosal, transdermal and epidural routes offer novel methods for administration of analgesic drugs and have considerable potential for improving techniques in feline pain management.
2J Small Anim Pract 2001 Dec;42(12):587-93
In order to access the PubMed abstract of this article, visit thiswebsite link.
3Journal of Feline Medicine and Surgery; 6(5), Oct 2004: 321-333
Meloxicam for Analgesia in Dogs
A clinical trial was conducted to evaluate the safety and efficacy of meloxicam in dogs with chronic osteoarthritis. A scoring system assessed specific lameness, general stiffness, painful rise, exercise intolerance, and behavior, and demonstrated significant reductions in clinical signs of osteoarthritis following 4 weeks of drug therapy. Side effects were minimal in extent and duration. The findings of this investigation suggest that the efficacy, tolerance, and formulation of meloxicam oral suspension make it well suited for the treatment of chronic osteoarthritis in the dog.
Can Vet J 2000 Apr;41(4):296-300
is a potent anti-inflammatory and analgesic which can be used for the management of surgical pain or chronic pain. The drug should not be given to animals with GI ulceration, impaired renal or hepatic function, or coagulation disorders. Ketoprofen should not be used preoperatively when noncompressible bleeding may be a problem. Occasional vomiting has been reported. When an NSAID or other drug that is potentially irritating to the GI tract is needed, topical preparations offer an excellent alternative. Pharmaceutical Research, Vol. 13, No. 1, 1996 reports (in humans) “a topical formulation of ketoprofen has been developed for the temporary relief of minor aches and pains of muscle and joints and to minimize gastrointestinal side effects after oral administration.”
POISONING / TOXICOSIS :Xylitol Poisoning in Dogs
Compounding pharmacists are now receiving requests from veterinarians to compound oral medications for dogs and cats in vehicles that are known to be free of xylitol. Xylitol is an artificial sweetener commonly used to sweeten human medications, gums, mouthwashes and candies, and while not toxic to humans, can be quite toxic to dogs. Xylitol is not absorbed from the gastrointestinal tract of humans, but is easily absorbed in dogs. Once in the bloodstream, xylitol acts like glucose, stimulating insulin secretion, which causes life-threatening hypoglycemia. Profound hypoglycemia can last for 1-2 hours following xylitol ingestion, and has frequently resulted in death. Many commercially available drugs labeled for humans, such as gabapentin oral suspension, contain xylitol as an inactive ingredient, and all human medications used in dogs should be scrutinized for xylitol content. Compounding pharmacists can play a valuable role for veterinarians and veterinary patients by providing xylitol-free suspensions of medications and by educating clients to avoid all xylitol-containing foods in their pets. It is not currently known if xylitol is toxic in cats, but for the present, xylitol must also be assumed to be toxic to cats. For more information, search “xylitol” at http://www.aspca.org.Apomorphine to Stimulate Vomiting
Emetic drugs are usually administered in emergency situations after ingestion of a toxin. “Apomorphine is an opiate drug that acts as a potent central dopamine agonist to directly stimulate the CTZ. It can be administered PO, IV, or SC; the IM route is not as effective. It can also be applied directly to conjunctival and gingival membranes, using the tablet formulation, which can easily be removed once emesis is initiated. Vomiting usually occurs in 5-10 min. Although apomorphine directly stimulates the CTZ, it has a depressant effect on the emetic center. Therefore, if the first dose does not induce emesis, additional doses are not helpful. Because the vestibular apparatus may also be involved in apomorphine-induced vomiting, animals that are sedate and motionless will not vomit as readily as animals that are active. Because it can cause CNS stimulation, apomorphine is used cautiously in cats. Opiate-induced excitement in cats can be treated with naloxone (an opiate antagonist).”
Apomorphine dosage for dogs: 4 mg/kg PO; 0.02 mg/kg IV; 0.3 mg/kg SC (from Merck Veterinary Manual, 8th edition, p. 1681); 0.25mg/kg (as a tablet) into the conjunctival sac (from Plumb’s Veterinary Drug Handbook, p.51)Accidental Poisoning
“is not a rare event; and veterinarians need to have access to antidotes. However, there are relatively few products specifically labeled for use in these instances, so it has not really been legal for veterinarians to have previously prepared antidotes for poisonings on hand in emergency rooms. For example, if a case of lead poisoning is diagnosed and the veterinarian needs some calcium EDTA as an antidote, there is no product available labeled for use in animals… Compounding offers opportunities for facilities to have [items such as calcium EDTA] on hand … for emergency treatment, in anticipation of a legitimate prescription.”
Intl J of Pharm Comp1997 July/Aug; 1(4): 240N-acetylcysteine as an Antidote for Acetaminophen Toxicosis
N-acetylcysteine (NAC) is the antidote of choice for the treatment of acetaminophen poisoning, one of the most common types of intoxication in dogs and cats. NAC acts principally by replenishment of intracellular glutathione stores and detoxification of the reactive metabolite (NAPQI). NAC acts as a scavenger of free radicals, blocks the conversion of hemoglobin to methemoglobin, and can reduce the extent of liver injury.Although NAC is most effective if administered less than 12 hours after ingestion of acetaminophen, the use of NAC as an antidote is still recommended up to 36 to 80 hours after acetaminophen ingestion.
Oral NAC, IV NAC, and IV sodium sulfate were evaluated as treatments for cats who had received toxic sublethal doses of acetaminophen (APAP). At the dosage levels used, oral NAC, IV NAC, and IV sodium sulfate were equally effective antidotes, as measured by decreased methemo-globinemia, increased whole blood reduced glutathione, decreased APAP half-lives, and increased urinary excretion of the APAP-sulfate conjugate. All the antidotal treatments produced results significantly different from those in the control cats.
To determine if rectally administered N-acetylcysteine (NAC) is absorbed into the systemic circulation, NAC was administered into the rectal vault (2.0 g/kg) of swine via a balloon-tipped Foley catheter inserted into the animals’ rectums. NAC administered via the rectal route resulted in systemic absorption as determined by spectrophotometric methods in 5 of the 7 study animals. This study provides important information regarding the development of a potential alternative route for the administration of NAC to dogs.
In dogs and cats, NAC can be administered intravenously or orally, but has a pungent odor. Oral administration of NAC typically causes nausea and vomiting. The oral solution can be compounded as a chicken-flavored preparation to improve palatability.
Rapid intravenous administration of NAC can cause hypotension, bronchospasm, and flushing. Reactions can be minimized by slowing the rate of infusion.
Activated charcoal may absorb NAC and reduce its effectiveness, so NAC should not be administered within two hours of giving activated charcoal. “Administration of activated charcoal may exacerbate vomiting and lead to aspiration. A strong antiemetic agent (metoclopramide 0.4 mg/kg IV) may be necessary to prevent emesis.”
NAC is currently not approved by the FDA for use in dogs and cats, but is available in human formulations, and upon a prescription order, can be compounded to meet specific veterinary needs.
Compendium 2003 Apr;25(4):276-280
Am J Vet Res 1985 Jul;46(7):1485-9
In order to access the PubMed abstract of this article, visit thiswebsite link.
Vet Hum Toxicol 1997 Dec;39(6):329-31
Vet Med 1997;92(2):158-165
Dimercaptosuccinic Acid for Lead Poisoning in Cats
Wright Veterinary Medical Center, Bethlehem, PA
The owners of two nine-year-old cats moved to a new house. One week after moving, both cats were vomiting and losing weight so the owners brought the cats to the veterinary clinic. The veterinarian began intravenous hydration. Blood work showed a very high level of nucleated RBC’s. The CBC revealed platelet clumps on feathered edge, few macrocytes, moderate anisocytosis, and occasional acanthocytes (54% and 45.1% NRBC). One cat had two seizures on the first day of hospitalization. Based on the initial signs and nucleated red cells, lead poisoning was suspected, although there was no radiographic evidence of lead ingestion. We tested for lead and began treatment with dimercaptosuccinic acid (DMSA) 40mg/cc.
The cats improved clinically within 24 hours. There were no more seizures and the cats began to eat. The blood lead levels were 164.8 and 210 (normal is 0-25). The cats were treated with 40mg (1cc) of DMSA given orally three times per day for a total of 10 days. DMSA is not commercially available in an injectable or liquid form. Therefore, we worked together with our compounding pharmacist to prepare a sterile formulation that would be suitable for intravenous or oral use.
The second day after therapy had begun, the owners informed us that they had been sanding the painted floors in their new house. The cats probably walked through the dust and in grooming themselves licked the lead paint off their paws. There have been no further problems with the cats to our knowledge. The owner declined to come in for a lead level recheck.
Penicillamine for Long-Term Treatment of Lead Poisoning
Penicillamine chelates a variety of metals, including copper, lead, iron and mercury, forming stable water-soluble complexes that are excreted by the kidneys. Used primarily for its chelating ability in veterinary medicine, it is the drug of choice for copper storage-associated hepatopathies in dogs at a dose of 15mg/kg PO twice daily. Penicillamine may also be used in cystine urolithiasis (penicillamine combines chemically with cystine to form a stable soluble complex that can be readily excreted) and in a different dose for the long-term oral treatment of lead poisoning. “This drug should preferably be given on an empty stomach, at least 30 minutes before feeding. If the animal develops problems with vomiting or anorexia, three remedies have been suggested. 1) Give the same total daily dose, but divide into smaller individual doses and give more frequently. 2) Temporarily reduce the daily dose and gradually increase to recommended dosage. 3) Give with meals (will probably reduce amount of drug absorbed).”
Veterinary Drug Handbook, 2nd edition, Donald C. Plumb, Ed.
4-Methylpyrazole for Ethylene Glycol (Antifreeze) Poisoning
Therapy for ethylene glycol poisoning is aimed at preventing absorption, increasing excretion, and preventing metabolism of ethylene glycol to its toxic metabolites. Inhibition of liver alcohol dehydrogenase (ADH), the enzyme responsible for the initial reaction in the metabolic pathway, can be accomplished by giving a compound that combines with the enzyme and renders it inactive. The most effective ADH inhibitor in the dog is 4-methylpyrazole (4-MP), which unlike most competitive inhibitors (ethanol, propylene glycol, and 1,3-butanediol) does not contribute to CNS depression and increased serum osmolality. The recommended dose of 5% (50mg/ml) 4-methylpyrazole is 20 mg/kg body weight IV initially, followed by 15 mg/kg IV at 12 and 24 hr, and 5 mg/kg at 36 hr. While 4-MP is the recommended therapy in dogs, it is not appropriate for use in cats. Although it is non-toxic, it does not effectively inhibit EG metabolism unless administered to a cat at the same time as consumption of EG.
Am J Vet Res 1995;56:825.
SEIZURE CONTROL :Potassium Bromide for Seizuresby Mollyann Holland, D.V.M., Oklahoma City, OK
Diplomate, American College of Veterinary Internal MedicinePotassium bromide is frequently helpful in treating refractory seizures in animals. Because potassium bromide is excreted renally, it may also be preferable for use in animals that have developed hepatotoxicity while on other anticonvulsants. My compounding pharmacist prepares this as a liver flavored solution, which can easily be administered to dogs. I feel that it is important to inform my animal owners that potassium bromide solution is compounded from a reagent grade chemical, and is not a commercially available “drug.”KBr is dosed on a weight basis. Maintenance doses range from 20-100 mg/kg body weight/day, and can be given as a single or divided dose. I usually dose at 30-40mg/kg/day as a single dose with food. Due to its long half-life, KBr can take up to four months to reach steady state; therefore, a loading dose may be required if therapeutic blood levels must be reached quickly. The loading dose is 400-600 mg/kg body weight and is administered orally over 30 to 60 minutes to avoid vomiting. A loading dose is not necessary if it is possible to keep the animal on other medications (as in a case of emerging hepatotoxicity) until levels of bromide are therapeutic (0.5-1.5 mg/ml), when the other anticonvulsant can be tapered off.
Potassium Bromide Chewable “Treats” for Seizure Control
Contributed by Steve Toney, R.Ph., Erin King, C.Ph.T. and Pam Woodin, D.V.M.
Case Report: 5 y.o. male Golden Retriever with seizure disorder. The owners called our compounding pharmacy to see what we could do as they were having difficulty administering medications to their dog. We suggested medicated canine treats that we have compounded many times with a 100% success rate. The veterinarian was consulted and we prepared potassium bromide (KBr) 150 mg treats coated with liver and beef flavored powder. The owner administers two treats two times daily, and the dog now loves to take his medicine!
Note: Chewable treats can be compounded to contain a variety of medications and flavored for the specific breed or pet. This dosage form has high patient acceptance and a low risk of owner misdosing.
Potassium bromide (KBr) can be also compounded as an oral solution which is easy to flavor and convenient for use as a loading dose. However, the risk of owner misdosing is greater than with a chewie or capsule.
Phenobarbital: Problems and Solutions
While phenobarbital is often used in veterinary medicine to treat seizure disorders, there are several concerns with its use:
- there are no commercially available veterinary approved products
- phenobarbital tablets for human use are small, hard, and unscored, making them difficult to divide for individualized dosing
- phenobarbital elixir has a high alcohol content, which is problematic for cats or any species when chronically administered
- phenobarbital induces CYP450 hepatic enzymes which can result in substantial drug interactions with oral anticoagulants, steroids, antibiotics, beta-blockers, theophylline, etc.
- phenobarbital is contraindicated in dogs with hepatic disease
When you wish to prescribe phenobarbital, please be aware that our compounding pharmacy can prepare an alcohol-free, appropriately flavored oral suspension, which is highly bio-available and very easy to use when administering a loading dose or when a flexible dose is needed. Once the maintenance dose is established, the dosage form can be switched to a capsule (with a lower risk of misdosing by the owner) or a flavored chewable medicated “treat”, with the added benefit of high patient acceptance.
UROLOGY : Treatment for Urinary Incontinence Hormonal Therapy:
Diethylstilbestrol (DES) has been used to treat estrogen responsive incontinence in spayed female dogs. The use of DES is contraindicated in cats as daily use has resulted in pancreatic, hepatic, and cardiac lesions.Dose for dogs:Initially 0.1-1.0 mg PO daily for 3-5 days, followed by maintenance therapy of approximately 1 mg PO per week. Some animals may require much higher initial dosages to obtain a response. DES can be given PO to female dogs at 0.1-0.3 mg/kg/day for 7-10 days, followed by a similar dose once weekly. Dogs should be maintained at the lowest possible dose because bone marrow suppression can develop when diethylstilbestrol is given in high doses. 1,4 When therapy is chronic or high dosages are used, packed cell volumes, white blood cell counts, and platelet counts should be done at least monthly. Liver function tests should be done at baseline, one month after therapy, and repeated 2 months after cessation of therapy if abnormal.
Clients should be informed to contact the veterinarian if signs and symptoms of lethargy, diarrhea, vomiting, abnormal discharge from vulva, excessive water consumption and urination or abnormal bleeding occur. DES is not for human consumption and should be dispensed only in child-resistant containers and stored in a secure location.1
DES is not currently commercially available; however, the medication can be prepared by a compounding pharmacy.
Phenylpropanolamine (PPA) is a weak alphaagonist that increases urethral sphincter tone and produces closure of the bladder neck, and is used to treat urethral sphincter hypotonus and resulting incontinence in dogs and cats.
Dogs: 1.1 mg/kg PO every 8 hours Cats: 12.5mg PO every 8 hours
The effect is short-lived, and the dose needs to be titrated to effect. “Dogs that are older at the onset of clinical signs (median 5 years) and those with a longer period from the time of ovariohysterectomy to the onset of urinary incontinence (median 2.5 years) respond best. PPA is preferred to ephedrine because side effects are less severe; ephedrine has greater cardiovascular side effects and it tends to lose effectiveness over time.”2 In a multicenter, blinded, placebo-controlled trial, 50 dogs that presented with clinical signs consistent with urinary sphincter mechanism incontinence were treated for 28 days with either PPA (1 mg/kg three times daily) or placebo. At day 28, 85.7 per cent of PPA-treated cases had no episodes of unconscious urination compared with 33.3 per cent of placebo-treated cases.3
Potential side effects include restlessness, irritability, hypertension and anorexia. Numerous drug interactions exist.
In November2000, human PPA preparations were removed from the market due to reports of serious side effects in humans. PPAcontinues to be available as a bulk chemical for veterinary use only.
1 Veterinary Drug Handbook, 3rd edition, Donald C. Plumb, ed. pp.193-5, and 508-9
2 Handbook of Veterinary Drugs, 2nd edition, pp. 277-8
3 J Small Anim Pract. 2002 Nov;43(11):493-6
In order to access the PubMed abstract of this article, visit thiswebsite link.
Per your prescription, we can compound customized dosage forms to meet the specific needs and flavor/texture preferences of each animal.
Piroxicam for Canine Bladder Cancer
Traditional chemotherapy (using cisplatin, carboplatin, adriamycin, and others) has been used in canine Transitional Cell Carcinoma (TCC). The response has been rather disappointing with <20% of dogs having remission.
Interest in non-steroidal anti-inflammatory (NSAID) therapy began when dogs with various forms of spontaneous cancer had remission while receiving the NSAID piroxicam for pain control, and no other therapy. Two of the first dogs treated (one with metastatic carcinoma, one with undifferentiated sarcoma) had advanced cancer and had remission of their cancer when only receiving piroxicam. This has led to numerous studies of piroxicam in animals with cancer at Purdue University Veterinary Teaching Hospital (PUVTH). In an attempt to improve the response of TCC to therapy, PUVTH conducted a study comparing chemotherapy (cisplatin) alone to chemotherapy plus piroxicam. The combination of cisplatin and piroxicam was more effective against the cancer, but the combination treatment caused a rise in BUN. In several instances, the cisplatin therapy was withdrawn (so as to not cause renal damage) while the tumors were still shrinking.
In a phase I study of piroxicam in 62 dogs with various histopathologically confirmed, measurable tumors, gastrointestinal toxicity was dose-related and dose limiting, but anti-tumor activity occurred at lower, less toxic doses of piroxicam. Partial remission occurred in 8 dogs, including 3 of 10 dogs with TCC. A phase II clinical trial of piroxicam in dogs with histologically confirmed, measurable, nonresectable TCC was performed. The dogs lived at home with their owners and were evaluated at the PUVTH at monthly intervals. Piroxicam was given orally at a dosage of 0.3 mg/kg every 24 hours (the accepted canine dosage prior to this trial). Tumor response in 34 dogs included 2 complete remissions (CR), 4 partial remissions (PR), 18 stable disease (SD), and 10 progressive disease (PD). Piroxicam therapy was generally well tolerated, with gastrointestinal toxicity noted in six dogs and renal papillary necrosis in two dogs. The median survival was 180 days. Fifty-five additional dogs were treated with piroxicam, and tumor response included 2 CR, 7 PR, 32 SD, and 14 PD.
It is not known how long dogs with TCC that are not treated will live. Survival is affected by the growth rate of the tumor, the exact location of the tumor within the bladder, and whether the tumor has metasticized. The median survival in dogs treated with cisplatin or carboplatin at PUVTH was 130 days. Median survival with piroxicam treatment in 55 dogs with TCC was 190 days. The survival times in all of these studies, however, vary tremendously from only a few days to more than one year. Longer survival times have been reached when chemotherapy is combined with piroxicam, but the optimal combination treatment is still being determined.
Cancer Chemother Pharmacol 1992;29:214-218
J Vet Intern Med 1994;8:273-278
Cancer Chemother Pharmacol 2000;46:221-226
In order to access the PubMed abstract of this article, visit thiswebsite link.
Urologic Oncology 2000;5:47-59
Citrate Salts as Alkalinizing Agents
Citrate salts are a source of bicarbonate, but are much more palatable than bicarbonate preparations. “They are used as urinary alkalinizers when an alkaline urine is desirable and in the management of chronic metabolic acidosis accompanied with conditions such as renal tubular acidosis or chronic renal insufficiency. Potassium citrate alone has been used for the prevention of calcium oxalate uroliths. The citrate can complex with calcium thereby decreasing urinary concentrations of calcium oxalate… When urine is alkalinized by citrate solutions, excretion of certain drugs (e.g. quinidine, amphetamines, ephedrine, …tetracycline) is decreased, and excretion of weakly acidic drugs (e.g. salicylates) is increased. The solubility of ciprofloxacin and enrofloxacin is decreased in an alkaline environment [and patients] should be monitored for signs of crystalluria.” (Plumb’s Veterinary Drug Handbook, 2nd ed.) In combination with potassium citrate preparations, these agents may lead to severe increases in serum potassium levels: NSAIDs, ACE-inhibitors, cyclosporine, digitalis, heparin and others.
Fludrocortisone is a long-acting corticosteroid with potent mineralocorticoid and moderate glucocorticoid activity. It is used in small animal medicine for the treatment of adrenocortical insufficiency, where it promotes sodium retention and urinary potassium secretion. It is commercially available only as the human product, a tablet containing 0.1 mg fludrocortisone acetate. The maintenance therapy for animals (particularly dogs) can require administration of multiple tablets for each daily dose. Therefore, it may be more convenient for owner and animal to administer fludrocortisone acetate as a flavored suspension, or single flavored solid dosage form.
Aluminum Hydroxide for Hyperphosphatemia
For dogs and cats, aluminum hydroxide is initially dosed at 30 – 90 mg/kg orally one to three times daily. A preparation that can be mixed with food may be preferred as it is more easily dispersed throughout ingesta. Dosage must be individualized, and serum phosphate levels should be evaluated at 10-14 days to determine optimum dosage.
Veterinary Drug Handbook, 3rd edition, Donald C. Plumb, editor. pp. 48-49
Calcitriol for Chronic Renal Failure
Submitted by Shirley Russman, D.V.M.
Our protocol for treating chronic renal failure includes a special diet, adequate hydration, potassium supplementation, stomach acid control and calcitriol therapy to control phosphorus levels. Calcitriol (a vitamin D3 metabolite) may also be used to prevent or reverse secondary hyperparathyroidism in dogs and cats with chronic renal failure.
Calcitriol is dosed in nanograms. Commercially available products are for humans, and the dose is much too high for dogs or cats (for example, the capsule contains 250 nanograms or 0.25 micrograms). Our compounding pharmacist has been able to prepare any capsule (8 nanograms and up) or liquid (i.e. 4 nanograms/0.25ml) necessary to meet our needs. We have used this compounded remedy over one hundred times and have found it to be very successful in lowering phosphorus levels in our patients with chronic renal failure. Serum calcium levels should be monitored as hypercalcemia is a possible consequence of calcitriol administration.
Calcitriol “has a rapid onset of action (1-4 days) and a short half-life (4-6 hours). Oral calcitriol is administered to patients after initial stabilization with fluid therapy, dietary protein and phosphorus restriction, the use of intestinal phosphate binders and H-2 blockers as needed. Serum phosphorus should be less than 6 mg/dL (1.9 mmol/liter) before initiating calcitriol.
“Hypercalcemia usually only occurs if calcitriol is used in conjunction with intestinal phosphate binders, especially calcium carbonate… Long-term use of phenytoin and the barbiturates may interfere with the action of the drug, necessitating higher doses of calcitriol… Thiazide diuretics may enhance the effects of calcitriol predisposing to hypercalcemia. Calcitriol-induced hypercalcemia may antagonize the antiarrhythmic effects of calcium channel-blocking agents.”
Handbook of Veterinary Drugs, 2nd edition, pp. 105-106
WOUND CARE :
Would you like a topical medication that is difficult for an animal to lick off or that will adhere to a mucosal surface?You can prescribe a medicated “polyox bandage” or “mucosal bandage”. When moistened, this medicated preparation will adhere to a wound or mucosal surface, thereby providing a protective barrier and increasing the contact between the medication and the affected area.Wound and Incision Care – Prevent Licking
A common problem encountered by veterinarians and animal owners is preventing an animal from licking an incision or licking medication from the area to which it has been applied. In addition to injury to the wound, pharmacists and veterinarians must consider the consequences of internal consumption of an external preparation. To prevent an animal from licking, a medication can be compounded to contain an extremely bitter substance. Choices include diphenhydramine, quinine, or the non-therapeutic ingredient sucrose octaacetate. Sucrose octaacetate can be added at 1% to 5% to any topical dosage form and the bitterness usually prevents the animal from repeated licking of the area of application. Another way to protect a medicated area from licking is to incorporate the needed medication into CAP (Cellulose Acetate Hydrogen Phthlate) solution. Since CAP solution does not dissolve in an acidic pH, the animal’s saliva does not remove it from the skin. CAP solution can also be sprayed directly onto a wound or over stitches to protect them.Phenytoin/Lidocaine Poly-Ox Bandage Used to Treat Leg Wound
Problem: Twenty-four hours after an automobile accident, an eight-month old female pit bull presented with a leg injury that appeared as if it would have difficulty healing. The dog had been hit by an automobile, which had scraped a hole in the right front leg. The wound, which extended from the elbow to the carpus, was approximately 3/4″ to 1” wide.
Treatment: The tissue of the leg was stabilized using tension-relieving sutures. Because the veterinarian had prior successful experiences with other cases involving wound care, she requested we compound a topical preparation consisting of 2% phenytoin and 2% lidocaine in a methylcellulose/polyoxyethylene (poly-ox) bandage for the dog. The animal underwent hydrotherapy twice daily and the compounded medication was applied just before bandaging was secured.
Outcome: The wound was completely healed after 2 months of therapy and the animal has full use of her leg with no visible ill effects. According to the veterinarian, the animal healed much quicker than usual due to the increased contact time of the medications and she was satisfied with the treatment process.
We have also used this compound with the same positive success on a degloved feline after its paw had been caught in a fence overnight.
Randy S. Carr, R.Ph., FIACP & Pamela Doskey, D.V.M.
Therapy for Severe Chemical Burns
by Barbara Espe, D.V.M., North Dakota
In April 1998, I was called to euthanize a 1 1/2 year old female miniature schnauzer that had been burned with hot water from the bath tub and washed in Woolite® 3-4 weeks earlier. The full thickness burns involved about 80% of the skin on the dorsal trunk from neck to tail and elbows to midthigh. The owners were using aloe vera to treat the burns and she had a severe infection, was emaciated (5 lb.) and had not eaten for one week. Since she had survived so long without treatment, I had the owners sign ownership over to me and I contacted the Central Dakota Humane Society. They agreed to take on this project despite the many hours of labor and the potential cost. The dog was immediately given an analgesic and antibiotics.
I literally stopped at the pharmacy with the dog so the compounding pharmacist could see what we were up against. At the pharmacist’s suggestion, a Poly-Ox bandage containing phenytoin base 2% and misoprostol 0.002% was compounded and applied in a layered manner. Telfa® pads were used to cover the wound, and a T-shirt was put on to protect the bandages. The dog started eating canned food that night and in several days she was eating four large cans of food daily. In addition to the Poly-Ox bandage, she remained on Cefadrops® and Rimadyl®. She seemed to be uncomfortable and analgesics did not appear to control her pain. The powder was returned to the pharmacy and lidocaine 2% was added. Although this helped somewhat, the dog was becoming non-compliant at the time of her dressing changes. The compound was again modified to contain bupivacaine 0.2% to obtain an extended analgesic effect. This was a significant improvement and therapy continued for several months. As healing occurred, the dog began to experience itching in the regranulated skin and wound areas. Diphenhydramine was given orally along with the Rimadyl® and we began rubbing her stretched skin with Emu oil to keep it moist. Shortly thereafter, the dog “became a schnauzer again.” Her activity level has increased greatly and we anticipate a complete recovery.
When I began treating this dog, I thought that skin grafting would be necessary. Due to the success of this therapy, no grafting will be needed. However, I don’t expect hair regrowth and the epithelium will remain scarred and easily bruised.
HORSES :Electrolyte Paste to Restore Fluid and Acid Base Balance in Horses
“Prolonged exercise in horses, particularly when performed in hot and humid conditions, brings about large fluid and electrolyte loses which, if not restored, may impair thermoregulatory responses and result in hyperthermia.” In horses, administration of oral rehydration solutions (ORS) is problematic, because many horses refuse to drink fluids containing electrolytes. Therefore, administration of ORS typically requires placement of a nasogastric tube with its inherent risks. An alternative is to give a concentrated electrolyte mixture as a paste. Leon et al. of Department of Veterinary Clinical Sciences, University of Sydney, NSW, Australia studied six Thoroughbred geldings to determine “whether oral administration of a concentrated electrolyte paste would promote the restoration of fluid, electrolyte, and acid base balance as well as fluid and electrolyte deficits induced by furosemide administration” (a standard model which induces significant contraction of plasma volume and consistent electrolyte deficit against which the effects of treatment could be measured).”As a general conclusion, horses that received concentrated electrolytes [and had free access] to water consumed more water, regained more weight, lost considerably less electrolytes in urine, and maintained plasma electrolyte concentrations and acid base balance closer to baseline values than did those that had ad libitum access to water only.” Administration of electrolyte paste provided a more practical source than supplementation using feed or salt blocks.Am J Vet Res1998 Jul;59(7):898-903In order to access the PubMed abstract of this article, visit thiswebsite link.
Progesterone for Estrus Induction in Mares
According to Robert R. Foss, DVM, progesterone in sesame oil, 150 mg per day, IM is equally as efficacious as altrenogest. The optimal formulation is the combination of progesterone and estradiol 17-beta; the addition of estradiol provides a greater feedback than progesterone alone, so cessation produces a more dramatic response. The estradiol is somewhat protective against exacerbation of endometritis. Dr. Foss commonly uses this combination at 150 mg progesterone and 10 mg estradiol 17-beta, IM, daily for 10 days. Estrus will usually begin in 6-8 days with ovulation around day 10-12. This combination has been effective in situations where altrenogest has failed.114th IL VMA Proceedings, February, 1996
Prednisone (Oral) Ineffective in Horses
Jackson et al. compared the effects of prednisone with environmental management to environmental management alone for the treatment of heaves (recurrent airway obstruction), and reported that oral prednisone has no additional benefit.1
To be effective, oral prednisone must be absorbed and metabolized to its active form prednisolone. Robinson et al. designed a study with two objectives: 1) to compare oral prednisone with intravenous dexamethasone for the treatment of horses with heaves; and 2) to measure serum prednisolone levels in horses after oral administration of prednisone and prednisolone. Each of five horses received five drug formulations (prednisone and prednisolone in tablet and liquid form, as well as intravenous prednisolone sodium succinate as a positive control, all at a dose of 2.2 mg/kg) in a Latin square design study. Severity of airway obstruction was measured, and there were no significant differences between prednisone administration and no medication at any time. Prednisolone was detectable in serum immediately after intravenous administration, peaking at around 1000 ng/ml at 12 min. Oral administration of prednisolone tablets or liquid yielded peak serum prednisolone concentrations of 377-1032 ng/ml at 30-45 min. When horses received oral prednisone tablets or liquid, prednisolone never reached detectable levels in the serum. The authors concluded, “In order for the drug prednisone to be effective after oral administration it must be absorbed from the gastrointestinal tract and converted to the active drug prednisolone by the liver. Although trace serum levels of prednisone were detected, prednisolone never appeared in the serum. Our data do not allow us to determine if prednisone is poorly absorbed, rapidly excreted, or not converted to prednisolone by the liver. However, it is clear that prednisone is unlikely to have any anti-inflammatory effect when administered by mouth. Oral administration of prednisolone is likely to be beneficial because it is rapidly absorbed and achieves serum levels close to those that result from intravenous administration.”2
Robert N. Oglesby, DVM (The Horseman’s Advisor, www.horseadvice.com) reports his reaction to hearing the above presentation at the November, 2000 meeting of the American Association of Equine Practitioners: “I was shocked and looking around me hundreds of other vets were also: oral prednisone doses are in every equine medicine text with many descriptions of its indications. Why has no one noticed the lack of effect before now? The reason is simple: no one believed it was possible that [prednisone] was not effective [in horses]. Its usefulness in other species was too well established… we did not even question its use. Looking back on it, it was the management changes that were responsible for the clinical improvement…”
1Equine Vet J 2000 Sep;32(5):432-8
2 AAEP Proceedings, Vol. 46, 2000, pp. 266-267
In order to access the PubMed abstract of this article, visit thiswebsite link.
We can compound prednisolone into the most appropriate dosage form, including oral pastes or “chewies” that horses will love!
In horses, a dose of 8.5 mg/kg orally two times daily is recommended for reducing the cytokine effects in endotoxemia. For the treatment of navicular disease, 6 g/day orally for 6 weeks should be used.
Compendium 23(7), July 2001, 603-4
Anti-Diarrheals for Foals & Horses
Treatment of diarrhea should always be based on establishing a diagnosis and correcting the basic cause. Anti-diarrheal products are not a substitute for adequate fluid and electrolyte therapy when dehydration or shock threatens. When the veterinarian deems anti-diarrheal therapy is appropriate, the following options may be considered.
According to James L. Becht, D.V.M., M.S., Diplomat ACVIM, preparations containing bismuth subsalicylate seem superior to those containing kaolin, pectin, or activated charcoal for treating the foal with diarrhea. Bismuth subsalicylate neutralizes bacterial toxins, has some antibacterial activity, and may exert an antisecretory effect. It can be administered at a dosage of 4 oz q 6h; darkened feces will result. If no effect is seen within 48 hours, continued administration is probably not indicated. (105th Ohio VMA).
Wendy E. Vaala, V.M.D., Diplomate ACVIM reports (ACVIM 16th Veterinary Medical Forum) that delayed gastric emptying and gastroduodenal dysmotility can be improved in some foals with metoclopramide (0.25-0.6 mg/kg, PO q4-6h), erythromycin (1.0-2.0 mg/kg PO q6h), or cisapride (10 mg/kg PO q6h). If colic, ileus, and gastric reflux are present, Dr. Vaala recommends an abdominal sonogram to rule out the presence of an intussusception prior to initiating prokinetic therapy. Diarrhea may be treated symptomatically with bismuth subsalicylate (1-2 ml/kg, PO, q4-6h) and may also respond to psyllium administration. Intestinal probiotics containing Lactobacillus bacteria … may be given to foals receiving antibiotics to help reestablish intestinal flora.
Adult horses may be treated with bismuth subsalicylate 1 oz per 8 kg of body weight PO TID-QID (Clark and Becht 1987).
Headshaking in Horses
may include additional signs such as nose rubbing, striking at the nose with the forelegs, or active avoidance of light, warmth, or wind on the face. Newton et al studied 20 mature horses with typical headshaking of 2 week to 7 year duration, and concluded that the etiopathology may be a trigeminal neuritis or neuralgia. In 12 of 20 horses, drug therapy was initiated. Cyproheptadine (CP) alone was ineffective but the addition of carbamazepine (CM) resulted in 80-100% improvement in 80% of cases within 3 to 4 days of beginning drug therapy. Seven cases were treated with a combination of CM (4 mg/kg, three to four times daily) and CP (0.2-0.5 mg/kg every 12 to 24 hours).
Carbamazepine alone has been effective in 88% of cases. Some headshaking horses have responded well to CM doses of 1.6 – 2.4 grams every six hours without apparent side effects. Horses are treated for 10 to 20 days and if they respond, the treatment is discontinued. If clinical signs of headshaking recur, treatment is restarted. In practice, there is a realistic possibility of controlling but not curing headshaking with carbamazepine therapy at the present time. Other studies have reported that cyproheptadine alone was beneficial in more than two thirds of treated horses.
Equine Vet J 2000 May;32(3):208-16
In order to access the PubMed abstract of this article, visit thiswebsite link.
Equine Vet J 1998 Nov;(27):28-9
In order to access the PubMed abstract of this article, visit thiswebsite link.
J Am Vet Med Assoc 2001 Aug 1;219(3):334-7
In order to access the PubMed abstract of this article, visit thiswebsite link.
Use of phenytoin to treat horses with Australian stringhalt
Aust Vet J. 1991 Jul;68(7):221-4 Click for abstract.
VET AVIAN :Antifungal Therapy for Avian Species
In avian species, the most frequent causes of infection have shifted from gram-negative bacteria to gram-positive bacteria and Candida(often non-albican) species. There is a decreased susceptibility of many non-albicans species to available antifungal drugs, perhaps as a consequence of nondiscriminate azole use.The efficacy of terbinafine has been improved when administered in combination with azoles for treatment of azole resistant oral candidiasis and aspergillosis. Because terbinafine was administered successfully in an African gray parrot at 15 mg/kg every 12 hours for 30 days without adverse effects, it may have potential for use in systemic aspergillosis in these azole-sensitive species. Caution should be used in avian patients with liver or renal disease.Veterinary Clin North Am Exot Anim Pract. 2003 May;6(2):337-50, viTreatment of a Systemic Fungal Infection in a Parrot with Itraconazole Flavored Suspension and Nebulized Clotrimazole
Submitted by Michael Briggs, Pharm.D.A Solomon Island Eclectus parrot, female aged 1.5 years, presented in a weakened state. Examination and culture revealed a systemic Aspergillus infection. Due to its significant cost as well as concern for the pet, the owner was highly motivated to treat the parrot.
Treatment posed a challenge because the parrot only eats brightly-colored foods, and there was no commercially available clotrimazole solution for nebulization for veterinary use. The veterinarian contacted the local compounding pharmacy to discuss how compounded medications might help solve this therapeutic dilemma. It was decided that an oral suspension flavored with equal parts orange, banana, and strawberry could mask the bitter flavor of itraconazole, and that a customized dosage (20mg/ml) could be compounded for the parrot. The veterinarian also prescribed clotrimazole 1% for nebulization.
The owner administered 0.2ml (4mg) of itraconazole suspension to the bird each day by mouth using an oral syringe. Therapy continued for three months. Clotrimazole 1% solution was nebulized (1ml BID to TID) by placing a pediatric nebulizer mask over the cooperative bird’s head. After 30 days, the bird still had a productive cough. Therefore, nebulizer therapy with clotrimazole continued after total resolution of signs and symptoms of infection, for a total of four months (one month after the oral itraconazole was finished).
The parrot fully recovered. This case represented the pharmacy’s first attempt at avian therapy, and was 100% successful. The same therapy was used later for another bird that also fully recovered from a systemic Aspergillus infection.
Enrofloxacin in Birds
Enrofloxacin is highly active against most gram-negative bacteria. Doses of 15 mg/kg orally twice daily have maintained effective drug concentrations in most of the psittacine species that have been tested. Senegal parrots have required TID dosing for moderately resistant organisms. Keven Flammer, DVM, Dip ABVP, reports successful treatment of E coli, Klebsiella, and Proteus infections. He states that oral administration is well tolerated, but that IM administration should be avoided, and never used for repeated dosing, due to irritation at the site of injection. The IM formulation can be given orally but is unpalatable, even when mixed with flavoring. Dr. Flammer notes that an oral suspension can be compounded and appropriately flavored.
10th U Wisc Exotic Pet Conf Procd 04:01
The Capsule Report, Small Animal/Exotic Edition Jan 2002;20, 10: page 3
Haloperidol for Feather-Plucking and Self-Mutilation
Neuropeptides, particularly dopamine, are implicated in many self-mutilating disorders. The 1993 Proceedings of the Association of Avian Veterinarians (pg. 119-120) reports the dopamine antagonist haloperidol is currently being used on cockatiels, lovebirds, ring-neck parakeets, African Greys, and several species of cockatoos and Amazon parrots. The indications for use in these birds have included severe feather plucking, mutilation of skin and muscle over the back, chest and legs, wing web mutilation, and Amazon foot necrosis syndrome. Side effects from the use of haloperidol have included depression, depressed appetite, excitability and anorexia. (In most birds, side effects disappeared after discontinuing the drug for several days and then retrying at a lower dose.) One study reported normal behavior was maintained “by administering haloperidol at approximately 0.4 mg/kg body weight/day for approximately seven months.”
Journal of Small Animal Practice 1993; 34:564-566
Haloperidol for Feather Plucking
by Stacie Fowler, D.V.M., Texas
Signalment: “Echo”, adult male Eclectus Parrot
Chief Complaint: Feather picking of 4-6 years duration
Diagnosis: Previous veterinarian had done numerous tests in 1993 to rule out medical causes of feather picking and the final diagnosis was psychological behavioral feather picking.
Feather Picking: This is a common syndrome in pet “parrot-type” birds that can have medical and/or psychological causes. It is important to rule out all medical causes of this condition before initiating psychotropic drug therapy. It is also important to institute appropriate dietary and environmental changes as well as behavioral therapy along with psychotropic drug use.
We welcome your questions and the opportunity to help you solve medication problems.
MISCELLANEOUS : Efficacy of oral supplementation with L-lysine in cats latently infected with feline herpesvirus
Maggs et al. of the College of Veterinary Medicine, University of Missouri examined the effects of orally administered L-lysine on clinical signs of feline herpesvirus type 1 (FHV-1) infection and ocular shedding of FHV-1 in latently infected cats. Fewer cats and eyes were affected by conjunctivitis, and onset of clinical signs of infection was delayed on average by 7 days in cats receiving L-lysine 400 mg once daily for 30 days, compared with cats in the control group. Significantly fewer viral shedding episodes were identified in the treatment group cats, compared with the control group cats. This dose caused a significant but short-term increase in plasma L-lysine concentration without altering plasma arginine concentration or inducing adverse clinical effects.
Am J Vet Res 2003 Jan;64(1):37-42 In order to access the PubMed abstract of this article, visit thiswebsite link.
Of the seven major human cough suppressants, only dextromethorphanis indicated for treating cough in small animals. If after reviewing the indications and contraindications, cough suppression is desired, the available human products must be screened carefully as a very limited number contain dextromethorphan without other potentially harmful ingredients. Typically, the dose in dogs and cats is 1 to 2 mg/kg three to four times daily. Human products are not flavored to an animal’s taste, and may require administering a significant volume (typical strength is 15 mg/5 ml) to adequately dose an average size dog.
Docusate (DSS) can be used to assist in the passage of hard or dry feces that may occur secondary to dehydration or use of opioid analgesics or metoclopramide. While capsules hide the bitter taste, they can not be divided for appropriate dosing in smaller animals. The recommended dose in dogs and cats is 2 mg/kg once daily. For more severe cases, appropriately dosed DSS enemas may offer an alternative to phosphate-solution enemas.
Merck Veterinary Manual, 8th Edition, pp. 1691
Ursodiol for Gallstones
The purpose of this study, reported in Am J Health-Syst Pharm (Vol. 52) was to prepare an oral dosage form of the bile acid ursodiol (also known as ursodeoxycholic acid) from commercially available capsules and to determine the short-term stability of this formulation. The formula used for this extemporaneous compound was found to be stable for up to 35 days.
Ursodiol in a Dog with Chronic Hepatitis
A dog with severe cholestasis secondary to chronic hepatitis was treated with ursodeoxycholic acid (ursodiol) orally. After 2 weeks of daily treatment, the dog was more active and had an improved appetite. Monthly serum biochemical determinations and analysis of individual bile acid profiles documented improvement in hepatobiliary tests and a marked reduction in the concentrations of potentially hepatotoxic endogenous bile acids. These effects were maintained for approximately 6 months.
J Vet Intern Med 1997 May-Jun;11(3):195-7 In order to access the PubMed abstract of this article, visit thiswebsite link.
Studies have found an extemporaneously compounded ursodiol suspension to be stable for up to 35 days refrigerated. This drug is well absorbed orally and enters the liver directly from the portal system, and is then secreted into bile. Ursodiol should be administered orally as the first-pass effect is vital for effectiveness.
Aminocaproic Acid for Degenerative Myelopathy (DM) in Dogs
DM appears with relative frequency only in the German Shepherd breed (GSD); confirmation of the diagnosis is important in other breeds before assuming that they have DM of GSD. During the past two decades, R.M. Clemmons, DVM, Ph.D., and other researchers at the University of Florida have provided important new insights into the pathoetiology of DM. Recently, they have found that when combined with the history, neurologic signs, CSF protein concentration and EMG, an elevated CSF acetylcholinesterase level helps confirm the diagnosis. It is increasingly clear that DM is caused by an autoimmune disease attacking the nervous systems of patients, leading to progressive neural tissue damage. In many respects, DM is similar to Multiple Sclerosis in human beings.
The Integrative Medical Approach to Treatment of Degenerative Myelopathy involves four basic approaches: 1) exercise, 2) dietary supplementation, 3) medication, 4) other supportive measures. Conventional medicine has little to offer patients with DM. On the other hand, use of exercise, certain vitamins and selected drugs have delayed or prevented progression of DM in many afflicted dogs.
Clemmons et al have found 2 medications which appear to prevent progression or result in clinical remission of DM in up to 80% of patients – aminocaproic acid (EACA) and n-acetylcysteine (NAC). They propose that circulating immune-complexes lead to endothelial cell damage in the vessels of the CNS. Subsequently, fibrin is deposited in the perivascular spaces. When this degrades (point of action of aminocaproic acid), inflammatory cells are stimulated to migrate into the lesions. The inflammatory cells release prostaglandins and cytokines (point of action of vitamin E and C) which lead to the activation of tissue enzymes and the formation of oxygen free-radicals (point of action of acetylcysteine) which, in turn, leads to tissue damage.They recommend giving EACA as a flavored solution, 500 mg orally every 8 hours. A “source for EACA is to have a compounding pharmacy make the solution from chemical grade EACA.” The only side effects that have been attributed to EACA have been occasional gastrointestinal irritation. This has presented a problem only in a few patients, typically those with pre-existing GI problems. The only known drug interaction is with high dose estrogen compounds.
N-Acetylcysteine is a potent anti-oxidant which has powerful neuroprotective effects. Clemmons et al give 75 mg/kg divided in 3 doses a day for 2 weeks; then, 3 doses every other day. The N-acetylcysteine must be diluted to a 5% solution; otherwise, it will cause stomach upset. “This new treatment is expensive unless purchased through compounding pharmacies.” NAC can produce vomiting (due to the sodium content of the pharmaceutical product, which requires high concentration of base to buffer) and may increase the bleeding time. Giving fresh ginger 30 minutes before NAC or administering NAC with food (or on a full stomach) often reduces this effect.
The chances of successful treatment are improved if the therapy is begun early in the course of DM rather than later. A response to the drugs should be evident within the first 7-10 days.
Chlorpromazine for Anti-Emesis
Chlorpromazine (Thorazine®) is a phenothiazine and works at the emetic center, the chemoreceptor trigger zone, and peripheral receptors; it is this veterinarian’s “all purpose anti-emetic of choice” for cats.1 Chlorpromazine may cause extrapyramidal symptoms in cats when administered at high doses. The drug may discolor urine pink or red-brown, cause mild sedation, and may potentiate hypotension in dehydrated patients. Phenothiazines should not be given within one month of worming with an organophosphate agent. The recommended oral doses in dogs and cats is 3.3 mg/kg PO one to four times daily. Due to extensive first pass metabolism2, it may be necessary to reduce the dose in animals with liver disease. A liquid concentrate can be appropriately flavored for dogs or cats.
1Todd R. Tams, DVM, Dip ACVIM in CA VMA C/E Conf Procd, 2000
2Veterinary Drug Handbook 3rd edition, Donald C. Plumb, ed.; pp. 129-30
Managing Anorexia in Uremic Dogs and Cats
H2-receptor antagonists (cimetidine, ranitidine, and famotidine) can be useful to reduce gastric acid secretion. Increased gastrin concentrations in serum during chronic renal failure may stimulate excessive secretion of gastric acid and cause ulcer formation. Some uremic dogs and cats dramatically increase their interest in food and food intake after therapy with an H2 blocker. According to a presentation at the Atlantic Coast Veterinary Conference by Dennis J. Chew, DVM, Dip and C.A. Buffington, DVM, some uremic animals may need this medication for an extended period of time (months to rest of their lives). Much of the experience of these veterinarians has been either with cimetidine at an initial dose of 10 mg/kg, followed by 5 mg/kg PO BID or famotidine at 1 mg/kg daily.
The Capsule Report, Vol. 19, No. 10, Jan. 2001
Doxycycline for Prophylaxis and Treatment of Osteoarthritis in Dogs
Prophylactic administration of doxycycline (a tetracycline) has markedly reduced the severity of canine osteoarthritis (OA) in weight-bearing regions of the medial femoral condyle, and therapeutic administration of oral doxycycline has been shown to reduce the severity of articular cartilage breakdown in various animal models of OA. This disease modifying effect is associated with reductions in the levels of active and total collagenase and gelatinase in articular cartilage of the involved joint.
A prospective, clinical study of eighty-one dogs with OA secondary to spontaneous cranial cruciate ligament (CCL) rupture concluded that doxycycline inhibits nitric oxide production in cartilage in dogs with CCL rupture, and that doxycycline may have a role in the treatment of canine OA. Dogs with OA secondary to CCL rupture were divided into 2 groups before surgery. The Doxy-CCL group (n = 35) received 3 to 4 mg/kg doxycycline orally every 24 hours for 7 to 10 days. The CCL group (n = 46) received no treatment. Synovial fluid, articular cartilage, synovial membrane, and CCL samples were collected during surgery or immediately after euthanasia from healthy dogs (control group). Total nitric oxide concentrations measured in cartilage were significantly lower in the Doxy-CCL group than in the CCL group, but were not different from those measured in the control group.
In another study, ten healthy adult mongrel dogs underwent transection of the left anterior cruciate ligament, which resulted in a marked decrease in bone mass, with increased osteoclastic activity and increased bone formation. Doxycycline treatment did not significantly affect either bone formation or bone resorption. The authors concluded that doxycycline protects against joint breakdown in this OA model via inhibition of matrix metalloproteinases in articular cartilage, rather than through an effect on subchondral bone.
Vet Surg 2001 Mar-Apr;30(2):132-9
In order to access the PubMed abstract of this article, visit thiswebsite link.
J Rheumatol 1996 Jan;23(1):137-42
In order to access the PubMed abstract of this article, visit thiswebsite link.
J Rheumatol Suppl 1995 Feb;43:149-51
In order to access the PubMed abstract of this article, visit thiswebsite link.
Vet Clin North Am Small Anim Pract 1997 Jul;27(4):863-81
Arthritis Rheum 1992 Oct;35(10):1150-9
In order to access the PubMed abstract of this article, visit thiswebsite link.
Cisapride: a Prokinetic Drug
Cisapride (Propulsid® – Janssen Pharmaceutica), was removed from the U.S. and Canadian markets by its manufacturer because of serious cardiac effects in humans. However, cisapride is now available as a bulk chemical for veterinary use only and can be compounded as per your prescription order.
Cisapride is chemically related to metoclopramide, but unlike metoclopramide, it does not cross the blood-brain barrier or have antidopaminergic effects or cause extrapyramidal reactions. Cisapride “is more potent and has broader prokinetic activity than metoclopramide, increasing the motility of the colon, esophagus (in cats and guinea pigs), stomach, and small intestine… [Cisapride] has been used in managing gastric stasis, idiopathic constipation, gastroesophageal reflux, and postoperative ileus in dogs and cats. Practitioners found cisapride especially useful in managing chronic constipation in cats with megacolon; in many cases, it alleviated or delayed the need for subtotal colectomy. Cisapride was also used in managing cats with hairball problems.”
“Cisapride appeared to be well tolerated by dogs and cats. Adverse reactions to cisapride have not been reported to the United States Pharmacopeia’s Veterinary Practitioners’ Reporting Program… Disorders of GI motility are common and frustrating clinical problems in dogs and cats. Cisapride, with its extensive prokinetic action, was a welcome addition to veterinary medicine.”
“Life after cisapride: Prokinetic drugs for small animals.” Patricia M. Dowling, DVM, MS, DACVIM, DACVCP Veterinary Medicine, September 2000, pp. 678-685
As a promotility agent: initially 0.5mg/kg three times daily
To reduce regurgitation associated with megaesophagus: 0.55mg/kg orally one to three times daily, no less than 30 minutes before feeding.
As an antiemetic: 0.1-0.5mg/kg orally every 8 hours.
For chronic constipation: initially, 2.5mg (for cats up to 10#) or 5mg
(cats 11-15#), or up to 7.5mg (for cats over 16#) three times daily, 30
minutes before food, in combination with stool softener and bulk agent.
Cisapride is contraindicated in patients in whom increased GI motility could be harmful (e.g., perforation, obstruction, GI hemorrhage). Absorption of other orally-administered drugs may be affected. Cisapride may enhance anticoagulants’ effects; additional monitoring and anticoagulant dosage adjustments may be required. Cisapride may enhance the sedative effects of benzodiazepines. Clients should be advised to monitor the animal and report any adverse effects.
Veterinary Drug Handbook, 3rd edition, Donald C. Plumb, editor. pp. 139-140
Cat and ferret owners continually search for specialized foods and treats that their pets will readily consume and will also be effective for hairball prevention or elimination. Call us for a customized, flavored hairball remedy for your patients!
In a study conducted at the Animal Health Unit and Gastrointestinal Sciences, University of Calgary, Alberta, ten healthy, intact, adult male sled dogs received either stanozolol tablets, 2 mg/dog PO, q12h, for 25 days or an intramuscular injection of stanozolol 25 mg on Days 7, 14, 21, and 28. A 15N amino acid (5.27 mmol) was infused intravenously into each dog on Day 0 (before stanozolol treatment) and on Day 31 (after stanozolol treatment). Both oral and injectable stanozolol resulted in significant increases in amino acid nitrogen retention compared to pretreatment values. Oral stanozolol increased nitrogen retention from 29.2 +/-8.2% to 50.3 +/- 9.2%, while stanozolol injection increased nitrogen retention from 26.6 +/- 9.9% to 67.0 +/- 7.5%. The nitrogen retention action of stanozolol may be beneficial in dogs under stress of surgical trauma and chronic disease.
In a separate blinded crossover trial at the College of Veterinary Medicine, Kansas State University, 22 castrated Beagles with experimentally induced chronic renal failure were treated with stanozolol. Cowan et al. concluded that for dogs with mild-to-moderate, nonuremic, experimentally induced, chronic renal failure, stanozolol had positive effects on nitrogen balance and lean body mass. Stanozolol did not have a significant effect on body fat, bone mineral content, or food consumption per kilogram of body weight.
Anabolic steroids such as stanozolol have been used to treat geriatric dogs. These drugs can increase nitrogen and mineral retention so that the body can better utilize dietary protein. As a result, the dog’s appetite may improve, resulting in more strength, energy, and weight gain. There is one reported case of the use of stanozolol (0.5 mg/kg, SQ, BID, PRN) to stimulate appetite in a rabbit. However, this class of drugs is not without potentially serious side-effects which must be considered before using them. Anabolic steroids should be used with caution in animals with heart, liver, or kidney problems, or in animals with breast or prostate cancer. Stanozolol should not be used in pregnant animals, during lactation, in young animals, or in male breeding animals. Anabolic steroids may increase the effects of warfarin and other anticoagulants.
In dogs, reported side effects are mainly androgenic, including increased aggression, increased activity, weight gain and mood alterations. However, in cats with and without chronic renal failure, there are reported cases of hepatotoxicity that appear to be related to the use of stanozolol.
J Am Vet Med Assoc. 1997 Sep 15;211(6):719-22
In order to access the PubMed abstract of this article, visit thiswebsite link.
Can J Vet Res. 2000 Oct;64(4):246-8
In order to access the PubMed abstract of this article, visit thiswebsite link.
Veterinary Forum. April 1999
In order to access the PubMed abstract of this article, visit thiswebsite link.
What is compounding?
Compounding that is consistent with the FDA Extra-Label Drug Use regulations is the customized manipulation of an approved drug(s) by a veterinarian, or by a pharmacist upon the prescription of a veterinarian, to meet the needs of a particular patient. For example, mixing two injectable drugs is compounding. Preparing a paste or suspension from crushed tablets is another example of compounding. Likewise, adding flavoring to a drug is compounding. Be aware, however, that products are being promoted to veterinarians under the guise of compounding that do not fit this definition. According to the FDA, legal compounding is not the formulation of preparations from bulk or raw active ingredients. Compounding should not be used as a way of circumventing the drug approval process or producing a product so it can be sold for less cost than an FDA-approved drug.
Federal Regulations to Follow
The FDA regulations and Compliance Policy Guide 608.400 “Compounding of Drugs for Use in Animals” describe specific circumstances under which FDA will either permit compounding for use in animals or may exercise its enforcement discretion:
- A valid Veterinarian-Client-Patient relationship exists.
- The health of an animal is threatened, or suffering or death may result from failure to treat.
- Compounding is performed by a licensed veterinarian or a licensed pharmacist on the order of a veterinarian within the scope of professional practice.
- There is no approved animal or human drug that, when used as labeled or in conformity with the extralabel drug use regulations, will, in the available dosage form and concentration, appropriately treat the condition diagnosed.
- Preparations are compounded from FDA-approved animal or human drugs. Nothing in the regulations permits compounding from bulk (raw pharmaceutical ingredient) drugs.
- Compounding from a human drug for use in food-producing animals is not permitted if an approved animal drug can be used for the compounding.
- For animals produced for human consumption, the veterinarian institutes procedures to assure the identity of treated animals, establishes a substantially extended withdrawal interval for the compounded preparation supported by appropriate scientific information, and ensures food safety. Compounding is not permitted if it results in violative food residue or any residue that may present a risk to public health.
- No drug may be compounded for food animals from drugs listed on the prohibited list (go to www.fda.gov/AnimalVeterinary/ and enter “530.41” in the search engine).
- Veterinarians comply with all aspects of the federal extralabel drug use regulations including record-keeping and labeling requirements.
- Adequate procedures and processes are followed that ensure the safety and effectiveness of the compounded product.
- The scale of compounding in advance of receiving prescriptions is limited and commensurate with the established need for compounded products.
- All relevant state laws relating to the compounding of drugs for use in animals are followed.
Compounding from Unapproved Substances
Federal regulations describe specific circumstances under which veterinarians, or pharmacists upon veterinarians’ prescriptions, are legally permitted to compound drugs for extralabel use in animals. Under these regulations, compounding for non-food animals may only be performed using FDA-approved animal or human drug products and only when there is no approved animal or human drug product available in the relevant dosage form and concentration to appropriately treat the diagnosed condition. Compounding from human drugs for use in food animals is not allowed if an approved animal drug can be utilized. However, veterinarians may occasionally face situations where they diagnose conditions for which no FDA-approved product is available for use to relieve the animal’s suffering or prevent the animal’s death. The current state of veterinary medicine requires products to treat many conditions in a number of different
species, some of which are known to have unique physiological characteristics. Although FDA considers it a violation of the Federal Food, Drug and Cosmetic Act, it acknowledges the need for compounding from bulk active or raw ingredients within certain areas of veterinary practice. For example, the FDA published a list of bulk drug substances for compounding and subsequent use in animals to which FDA would exercise enforcement discretion and not ordinarily object, specifically poison antidotes available only as bulk chemicals. In these situations or others, veterinarians may find it necessary to compound, or prescribe for a pharmacist to compound, from the bulk chemical to satisfy the requirements of good veterinary medical practice. The veterinarian and/or pharmacist are then responsible for the safety and efficacy of the compounded drug. In cases where no approved drug or combination of approved drugs can adequately address a specific patient’s need, veterinarians and pharmacists must carefully assess whether the use of an
unapproved substance in a compounded veterinary drug is consistent with state and federal law and FDA policy.
Compounded Preparations are not Generic Drug Products
Generic drug products are very different from compounded preparations. Generic drug products are FDA-approved, which requires a demonstration of bioequivalence of safety and efficacy with the pioneer drug product. Generic animal drug products are identified by an Abbreviated New Animal Drug Application (ANADA) number on their label or in FDA drug references. In contrast to generic drugs, compounded preparations lack FDA approval.
How to Identify an FDA-Approved Animal Drug Product
FDA-approved animal drug products can be identified by the six-digit New Animal Drug Application (NADA) number for brand-name drug products or the six-digit ANADA number for generic drug products. The NADA or ANADA number and the statement “Approved by FDA” can usually be found on the drug product’s label including the package insert. It may also be helpful to cross-check with a drug reference, such as the FDA’s online databases, Animal Drugs @ FDA and FDA Orange Book, which list approved animal and human drug products,
respectively. The presence of a National Drug Code (NDC) number on a
product label does not confer FDA approval.
Inappropriate Compounding Pharmacy Practices Include the Following:
- Compounded preparations that mimic FDA-approved drug products.
Beware of pharmacies that purport to sell compounded preparations that are the same as commercially available FDA-approved products or similar but with a minor difference, such as a slightly different concentration. Often these are marketed as a cheaper alternative to the approved drug. FDA has not identified price as a legitimate reason for prescribing a compounded preparation. Legitimate compounding is prescription-driven and predicated upon the need to customize a preparation to meet an individual patient’s needs.
- Manufacturing under the guise of compounding.
The use of commercial scale equipment and preparation of large quantities of compounded products in anticipation of receiving orders.
- Promotion and advertising of unapproved new animal drugs.
FDA considers products compounded from bulk active ingredients to be unapproved new animal drugs.
- Wholesale distribution of compounded preparations.
It is not legal for compounded preparations to be developed in large quantities and sold to third parties (including veterinarians and companies) or wholesalers, to resell to individual patients.
Questions To Ask Your Pharmacist
Q: What are your credentials for preparing compounds for use in animals?
A: Pharmacy undergraduate education offers varying degrees of compounding instruction, and training in veterinary pharmacotherapy may be limited. Postgraduate pharmacy training can include continuing education certificates and membership in veterinary pharmacy professional organizations. Consider whether the pharmacy is compliant with United States Pharmacopeia (USP) standards, such as General Chapters <795> and <797> for compounding medications for both humans and animals.
Q: Are you licensed as a pharmacy in my state? Is the pharmacy accredited by an independent body?
A: Most state boards of pharmacy require that an out-of-state pharmacy register with their state prior to filling prescriptions to be mailed into their state. Veterinarians can inquire with their state board of pharmacy to ascertain the status of a pharmacy’s license and to gain valuable information including the pharmacy permit number. Also, consider whether the pharmacy is certified by an independent body. Examples include the National Association of Boards of Pharmacy’s Vet-VIPPS and the Pharmacy Compounding Accreditation Board.
Q: What sources will you use for the components and formula for the compound I am prescribing?
A: FDA-approved products should be used to make compounded preparations. In cases where no approved drug or combination of approved drugs can adequately address a specific patient’s need, veterinarians and pharmacists must carefully assess whether the use of an unapproved substance in a compounded veterinary drug is consistent with state and federal law and FDA policy. If medical necessity dictates that a bulk active ingredient be used in the formulation, the pharmacist should ensure the integrity of all components used (e.g. certificates of analysis, USP National Formulary grade substance, or substances obtained from an FDA-registered supplier.) The pharmacist can also identify the company from which products are purchased as well as the domestic or international location of the company. Formulas used for compounding should be obtained from a peer-reviewed source (e.g. published studies in primary literature, textbooks, or the USP) when possible.
Q: What assurances can be offered regarding the quality and stability of the preparation?
A: There are both benefits and risks associated with compounded preparations used in animals. While they may be useful when medically necessary, the reality is that no assurances can be given without sufficient scientific data backing the preparation method of each active ingredient. However, some assurances of the quality of active ingredients and preparation methods can be offered by the pharmacy to help mitigate certain risks that are also associated with compounding, such as poor quality ingredients or unstable preparations.
Q: How do I know that the compounded preparations such as drug delivery systems or drug combinations will be safe and effective?
A: You don’t. There is no assurance, like there is with an FDA-approved drug, that a compounded preparation will be safe or effective for the condition you are treating. Extensive laboratory and clinical studies are needed to assure that these preparations achieve adequate blood and tissue levels on a consistent basis from batch to batch as well as being safe to the animal. Sponsors of FDA approved products must conduct in vivo pre-market testing. Veterinarians should seek results from scientifically designed studies demonstrating the efficacy and safety of a particular preparation, including drug delivery systems in the target species. These study results showing suitable stability, relative efficacy, and safety in the target species can be considered in the benefit-risk analysis a veterinarian performs when deciding whether to use the particular preparation in the patient.
Q: What data or other sources will you use for the assigned beyond-use date for the compound I am prescribing?
A: Veterinarians should inquire as to how the beyond-use date was established. Beyond-use dates and expiration dates are not the same. Expiration dates for the chemical and physical stability of manufactured products are determined from results of rigorous analytical and performance testing, and they are specific for a particular formulation in its container and at stated exposure conditions. According to the USP (e.g. General Chapters <795> and <797>), the compounding pharmacist is responsible for setting the beyond-use date within the conservative default parameters established by USP.
Q: Will you prepare a compound specifically for my patient, or is it prepared in advance?
A: Pharmacies should compound medications pursuant to the receipt of a valid prescription.
Q: How would I report an adverse event that I think is associated with use of a compounded preparation?
A: Veterinarians should report suspected adverse events or product failures involving compounded preparations to the compounding pharmacist, the State Board of Pharmacy and the FDA Center for Veterinary Medicine. Instructions for reporting adverse events to FDA can be found at the FDA website:
Pharmacists should instruct pet owners to contact both the prescribing veterinarian and pharmacist immediately if a compounded preparation has caused an adverse event.
|Characteristics||Benefit||FDA Approved Drug Product: New Animal Drug (NADA) / Generic Animal Drug (ANADA)||Compounded Drug|
|FDA approval|| Agency substantiation of manufacturers’ drug label
claims that are supported with substantial scientific
evidence and language that are sufficiently
clear to ensure safe and effective use of the product.
|Tested in labeled animal species in laboratory and field trials||Drug’s safety and efficacy must be scientifically demonstrated||Yes||No|
| Manufactured according to
current Good Manufacturing Practices (cGMPs)
|Ensures each batch is manufactured within
specification for therapeutic consistency
|Manufacturing facilities inspected and approved by FDA||Ensures manufacturer compliance with FDA
regulations governing product quality
|Ongoing stability testing of drugs||Ensures drug shelf life matches labeled expiration date||Yes||No|
|Prescription drug advertising and promotional material submitted to and reviewed by FDA||Means nothing is false or misleading about the materials||Yes||No|
|Adverse events or lack of efficacy
reported to FDA
|Permits unanticipated yet significant post-marketing experiences to be communicated back from FDA to the veterinarian||Yes||Yes|
|Analytical testing of product prior to release for||Ensures that product contains what is represented on the label|
- FDA Center for Veterinary Medicine
- FDA Extralabel Drug Use Rules (21 CFR 530.3, 530.20, 530.41)
- CPG Sec. 608.400 Compounding of Drugs for Use in Animals
- Animal Drugs @ FDA
- Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations
- United States Pharmacopeia National Formulary (USP-NF)
- Papich, MG. Drug Compounding for Veterinary Patients.
AAPS J 2005; 07(02):E281-E287
- National Association of Boards of Pharmacy – http://www.nabp.net
- American Veterinary Medical Association – http://www.avma.org
- American Association of Bovine Practitioners – http://www.aabp.org
- American Association of Equine Practitioners – http://www.aaep.org
- Pharmacy Compounding Accreditation Board – http://www.pcab.info
- American Association of Feline Practitioners – http://www.catvets.com